News and commentary on the autism epidemic and my beautiful boy who is living with autism.

June 14, 2007

"No Evidence of Any Link"

2.0

7/24/13:
When I initially posted this page with just over a dozen studies, I
never thought it would become THE de facto place people would come to
see the body of evidence that shows that vaccines can cause autism.
So after six years and who knows how many views, I have updated
and reformatted the page to make a little more sense, with all the
full abstracts.

It is up to [EDIT] 96 papers now, but will always keep
adding.

Never
let anyone tell you that there is no evidence of any link between
vaccines and autism. MOST of the research into the matter shows
that there is.

The
original copy of the page (when it was around 60 studies) can be
found here.Research
supporting Vaccine/Autism Causation

Division of Epidemiology and Surveillance, Vaccine Safety
and Development Branch, National Immunization Program, Centers for
Disease Control and Prevention. 1999.

Thomas M. Verstraeten,
R. Davies, D. Gu, F DeStefano

Background: Concern has risen
on the presence of the ethylmercury containing preservative
thimerosal in vaccines. We assessed the risk for neurologic and
renal impairment associated with past exposure to
thimerosal-containing vaccine using automated data from the Vaccine
Safety Data link (VSD). VSD is a large linked database from four
health maintenance organizations in Washington, Oregon and
California, containing immunization, medical visit and demographic
data on over 400,000 infants born between '91 and '97.

Methods:
We categorized the cumulative ethylmercury exposure from Thimerosal
containing vaccines after one month of life and assessed the
subsequent risk of degenerative and developmental neurologic
disorders and renal disorders before the age of six. We applied
proportional hazard models adjusting for HMO, year of birth, and
gender, excluding premature babies.

Results: We identified
286 children with degenerative and 3702 with developmental
neurologic disorders, and 310 with renal disorders. The relative
risk (RR) of developing a neurologic development disorder was 1.8 (
95% confidence intervals [CI] =1.1-2.8) when comparing the highest
exposure group at 1 month of age (cumulative dose> 25 ug) to the
unexposed group. Within
this group we also found an elevated risk for the following
disorders: autism (RR 7.6, 95% Cl = 1.8-31.5),
non organic sleep disorders (RR 5.0, 95% Cl = 1.6-15.9}, and speech
disorders (RR 2.1, 95% (1=1.1-4.0). For the neurologic degenerative
and renal disorders group we found no significantly increased risk
or a decreased risk.

Conclusion: This
analysis suggests that high exposure to ethyl mercury from
thimerosal-containing vaccines in the first month of life increases
the risk of subsequent development of neurologic development
impairment,
but not of neurologic degenerative or renal impairment. Further
confirmatory studies are needed.

AbstractPURPOSE:
Universal newborn immunization with hepatitis B vaccine was
recommended in 1991; however, safety findings are mixed. The Vaccine
Safety Datalink Workgroup reported no association between hepatitis
B vaccination at birth and febrile episodes or neurological adverse
events. Other studies found positive associations betweenhepatitis
B vaccination and ear infection, pharyngitis, and chronic arthritis;
as well as receipt of early intervention/special education services
(EIS); in probability samples of U.S. children. Children with
autistic spectrum disorder (ASD) comprise a growing caseload for
EIS. We evaluated the association between hepatitis B vaccination of
male neonates and parental report of ASD.METHODS:
This cross-sectional study used U.S. probability samples obtained
from National Health Interview Survey 1997-2002 datasets. Logistic
regression modeling was used to estimate the effect of neonatal
hepatitis B vaccination on ASD risk amongboys age 3-17 years with
shot records, adjusted for race, maternal education, and two-parent
household.RESULTS:Boyswho
received the hepatitis B vaccine during the first month of life had
2.94 greater odds for ASD (nZ31 of 7,486; OR Z 2.94; p Z 0.03; 95%
CI Z 1.10, 7.90)compared
to later- or unvaccinated boys.Non-Hispanicwhite boys were 61%less
likely to haveASD(ORZ0.39; pZ0.04; 95% CIZ0.16, 0.94) relative to
non-white boys.CONCLUSION:Findings
suggest that U.S. male neonates vaccinated with hepatitis B vaccine
had a 3-fold greater risk of ASD; risk was greatest for non-white
boys.

Do
aluminum vaccine adjuvants contribute to the rising prevalence of
autism?J
Inorg Biochem. 2011 Nov;105(11):1489-99. Epub 2011 Aug
23.Tomljenovic
L, Shaw CA.Neural
Dynamics Research Group, Department of Ophthalmology and Visual
Sciences, University of British Columbia, 828 W. 10th Ave,
Vancouver, BC, Canada V5Z 1L8.AbstractAutism
spectrum disorders (ASD) are serious multisystem developmental
disorders and an urgent global public health concern. Dysfunctional
immunity and impaired brain function are core deficits in ASD.
Aluminum (Al), the most commonly used vaccine adjuvant, is a
demonstrated neurotoxin and a strong immune stimulator. Hence,
adjuvant Al has the potential to induce neuroimmune disorders. When
assessing adjuvant toxicity in children, two key points ought to be
considered: (i) children should not be viewed as "small adults"
as their unique physiology makes them much more vulnerable to toxic
insults; and (ii) if exposure to Al from only few vaccines can lead
to cognitive impairment and autoimmunity in adults, is it
unreasonable to question whether the current pediatric schedules,
often containing 18 Al adjuvanted vaccines, are safe for children?
By applying Hill's criteria for establishing causality between
exposure and outcome we investigated whether exposure to Al from
vaccines could be contributing to the rise in ASD prevalence in the
Western world. Our results show that: (i) children from countries
with the highest ASD prevalence appear to have the highest exposure
to Al from vaccines; (ii) the increase in exposure to Al adjuvants
significantly correlates with the increase in ASD prevalence in the
United States observed over the last two decades (Pearson r=0.92,
p<0.0001); and (iii) a significant correlation exists between the
amounts of Al administered to preschool children and the current
prevalence of ASD in seven Western countries, particularly at
3-4months of age (Pearson r=0.89-0.94, p=0.0018-0.0248).The
application of the Hill's criteria to these data indicates that the
correlation between Al in vaccines and ASD may be causal.Because
children represent a fraction of the population most at risk for
complications following exposure to Al, a more rigorous evaluation
of Al adjuvant safety seems warranted.

Over
the last 200 years, mining, smelting, and refining of aluminum (Al)
in various forms have increasingly exposed living species to this
naturally abundant metal. Because of its prevalence in the earth’s
crust, prior to its recent uses it was regarded as inert and
therefore harmless. However, Al is invariably toxic to living systems
and has no known beneficial role in any biological systems. Humans
are increasingly exposed to Al from food, water, medicinals,
vaccines, and cosmetics, as well as from industrial occupational
exposure. Al disrupts biological self-ordering, energy transduction,
and signaling systems, thus increasing biosemiotic entropy. Beginning
with the biophysics of water, disruption progresses through the
macromolecules that are crucial to living processes (DNAs, RNAs,
proteoglycans, and proteins). It injures cells, circuits, and
subsystems and can cause catastrophic failures ending in death. Al
forms toxic complexes with other elements, such as fluorine, and
interacts negatively with mercury, lead, and glyphosate. Al
negatively impacts the central nervous system in all species that
have been studied, including humans. Because of the global impacts of
Al on water dynamics and biosemiotic systems, CNS disorders in humans
are sensitive indicators of the Al toxicants to which we are being
exposed.

Autoimmunity
to the central nervous system (CNS), especially to myelin basic
protein (MBP), may play a causal role in autism, a
neurodevelopmental disorder. Because many autistic children harbor
elevated levels of measles antibodies, we conducted a serological
study of measles-mumps-rubella (MMR) and MBP autoantibodies. Using
serum samples of 125 autistic children and 92 control children,
antibodies were assayed by ELISA or immunoblotting methods. ELISA
analysis showed a significant increase in the level of MMR
antibodies in autistic children. Immunoblotting analysis revealed
the presence of an unusual MMR antibody in 75 of 125 (60%) autistic
sera but not in control sera. This antibody specifically detected a
protein of 73-75 kD of MMR. This protein band, as analyzed with
monoclonal antibodies, was immunopositive for measles hemagglutinin
(HA) protein but not for measles nucleoprotein and rubella or mumps
viral proteins. Thus the MMR antibody in autistic sera detected
measles HA protein, which is unique to the measles subunit of the
vaccine. Furthermore, over 90% of MMR antibody-positive autistic
sera were also positive for MBP autoantibodies, suggesting a strong
association between MMR and CNS autoimmunity in autism. Stemming
from this evidence, we suggest that an
inappropriate antibody response to MMR, specifically the measles
component thereof, might be related to pathogenesis of autism.

AbstractThe etiology of
autoimmune diseases is still not clear but genetic, immunological,
hormonal and environmental factors are considered to be important
triggers. Most often autoimmunity is not followed by clinical
symptoms unless an additional event such as an environmental factor
favors an overt expression. Many environmental factors are known to
affect the immune system and may play a role as triggers of the
autoimmune mosaic.Infections: bacterial, viral and parasitic
infections are known to induce and exacerbate autoimmune diseases,
mainly by the mechanism of molecular mimicry. This was studied for
some syndromes as for the association between SLE and EBV infection,
pediatric autoimmune neuropsychiatric disorders associated with
streptococcal infection and more. Vaccines, in several reports were
found to be temporally followed by a new onset of autoimmune
diseases. The same mechanisms that act in infectious invasion of the
host, apply equally to the host response to vaccination. It has been
accepted for diphtheria and tetanus toxoid, polio and measles
vaccines and GBS. Also this theory has been accepted for MMR
vaccination and development of autoimmune thrombocytopenia, MS has
been associated with HBV vaccination. Occupational and other
chemical exposures are considered as triggers for autoimmunity. A
debate still exists about the role of silicone implants in induction
of scleroderma like disease.Not only foreign chemicals and agents
have been associated with induction of autoimmunity, but also an
intrinsic hormonal exposure, such as estrogens. This might explain
the sexual dimorphism in autoimmunity.Better understanding of these
environmental risk factors will likely lead to explanation of the
mechanisms of onset and progression of autoimmune diseases and may
lead to effective preventive involvement in specific high-risk
groups. So by diagnosing a new patient with autoimmune disease a
wide anamnesis work should be done.

AbstractThe aim of this
study was to investigate a previously overlooked, universally
introduced environmental factor, fetal and retroviral contaminants
in childhood vaccines, absent prior to change points (CPs) in
autistic disorder (AD) prevalence with subsequent dose-effect
evidence and known pathologic mechanisms of action. Worldwide
population based cohort study was used for the design of this study.
The United States, Western Australia, United Kingdom and Denmark
settings were used. All live born infants who later developed
autistic disorder delivered after 1 January 1970, whose redacted
vaccination and autistic disorder diagnosis information is publicly
available in databases maintained by the US Federal Government,
Western Australia, UK, and Denmark. The live births, grouped by
father’s age, were from the US and Australia. The children
vaccinated with MMRII, Varicella and Hepatitis A vaccines varied
from 19 to 35 months of age at the time of vaccination. Autistic
disorder birth year change points were identified as 1980.9, 1988.4
and 1996 for the US, 1987 for UK, 1990.4 for Western Australia, and
1987.5 for Denmark. Change points in these countries corresponded to
introduction of or increased doses of human fetal cell
line-manufactured vaccines, while no relationship was found between
paternal age or Diagnostic and Statistical Manual (DSM) revisions
and autistic disorder diagnosis. Further, linear regression revealed
that Varicella and Hepatitis A immunization coverage was
significantly correlated to autistic disorder cases. R software was
used to calculate change points. Autistic
disorder change points years are coincident with introduction of
vaccines manufactured using human fetal cell lines, containing fetal
and retroviral contaminants, into childhood vaccine regimens. This
pattern was repeated in the US, UK, Western Australia and Denmark.
Thus, rising autistic disorder prevalence is directly related to
vaccines manufactured utilizing human fetal cells. Increased
paternal age and DSM revisions were not related to rising autistic
disorder prevalence.

A
Positive Association found between Autism Prevalence and Childhood
Vaccination uptake across the U.S. PopulationJournal
of Toxicology and Environmental Health, Part A: Current
IssuesVolume
74, Issue 14, 2011, Pages 903 - 916Author:
Gayle DeLongaAbstractThe
reason for the rapid rise of autism in the United States that began
in the 1990s is a mystery. Although individuals probably have a
genetic predisposition to develop autism, researchers suspect that
one or more environmental triggers are also needed. One of those
triggers might be the battery of vaccinations that young children
receive. Using regression analysis and controlling for family income
and ethnicity, the relationship between the proportion of children
who received the recommended vaccines by age 2 years and the
prevalence of autism (AUT) or speech or language impairment (SLI) in
each U.S. state from 2001 and 2007 was determined. A positive and
statistically significant relationship was found: The higher the
proportion of children receiving recommended vaccinations, the
higher was the prevalence of AUT or SLI. A 1% increase in
vaccination was associated with an additional 680 children having
AUT or SLI. Neither parental behavior nor access to care affected
the results, since vaccination proportions were not significantly
related (statistically) to any other disability or to the number of
pediatricians in a U.S. state.The
results suggest that although mercury has been removed from many
vaccines, other culprits may link vaccines to autism.Further
study into the relationship between vaccines and autism is
warranted. To read the abstract click HERE.

Neonatal
administration of a vaccine preservative, thimerosal, produces
lasting impairment of nociception and apparent activation of opioid
system in rats.Brain
Res. 2009 Dec 8;1301:143-51. Epub 2009 Sep 9.Olczak
M, Duszczyk M, Mierzejewski P, Majewska MD. Department of
Pharmacology and Physiology of the Nervous System, Institute of
Psychiatry and Neurology, Warsaw, Poland.AbstractThimerosal
(THIM), an organomercury preservative added to many child vaccines
is a suspected factor in pathogenesis of neurodevelopmental
disorders. We examined the pharmacokinetics of Hg in the brain,
liver and kidneys after i.m. THIM injection in suckling rats and we
tested THIM effect on nociception. THIM solutions were injected to
Wistar and Lewis rats in a vaccination-like mode on PN days 7, 9, 11
and 15 in four equal doses. For Wistar rats these were: 12, 48, 240,
720, 1440, 2160, 3000 microg Hg/kg and for Lewis: 54, 216, 540 and
1080 microg Hg/kg. Pharmacokinetic analysis revealed that Hg from
THIM injections accumulates in the rat brain in significant amounts
and remains there longer than 30 days after the injection. At the
6th week of age animals were examined for pain sensitivity using the
hot plate test. THIM treated rats of both strains and sexes
manifested statistically significantly elevated pain threshold
(latency for paw licking, jumping) on a hot plate (56 degrees C).
Wistar rats were more sensitive to this effect than Lewis rats.
Protracted THIM-induced hypoalgesia was reversed by naloxone (5
mg/kg, i.p.) injected before the hot plate test, indicative of
involvement of endogenous opioids. This was confirmed by augmented
catalepsy after morphine (2.5 mg/kg, s.c.) injection. Acute THIM
injection to 6-week-old rats also produced hypoalgesia, but this
effect was transient and was gone within 14 days.Present
findings show that THIM administration to suckling or adult rats
impairs sensitivity to pain, apparently due to activation the
endogenous opioid system.

Thimerosal
is a vaccine antimicrobial preservative which has long been suspected
an iatrogenic factor possibly contributing to neurodevelopmental
disorders including autism. The association between infant vaccine
thimerosal exposure and autism remains an open question. Although
thimerosal has been removed from mandatory childhood vaccines in the
United States, thimerosal-preserved vaccines are still widely used
outside of the United States especially in developing countries.
Notably, thimerosal-containing vaccines are being given to the
newborns within the first 12-24 h after birth in some countries. To
examine the possible neurotoxic effects of early neonatal exposure to
a higher level of thimerosal, FVB mice were subcutaneously injected
with thimerosal-mercury at a dose which is 20× higher than that used
for regular Chinese infant immunization during the first 4 months of
life. Thimerosal-treated mice exhibited neural development delay,
social interaction deficiency, and inclination of depression.
Apparent neuropathological changes were also observed in adult mice
neonatally treated with thimerosal. High-throughput RNA sequencing of
autistic-behaved mice brains revealed the alternation of a number of
canonical pathways involving neuronal development, neuronal synaptic
function, and the dysregulation of endocrine system. Intriguingly,
the elevation of anterior pituitary secreting hormones occurred
exclusively in male but not in female thimerosal-treated mice,
demonstrating for the first time the gender bias of
thimerosal-mercury toxicity with regard to endocrine system. Our
results indicate that higher dose of neonatal thimerosal-mercury (20×
higher than that used in human) is capable of inducing long-lasting
substantial dysregulation of neurodevelopment, synaptic function, and
endocrine system, which could be the causal involvements of
autistic-like behavior in mice.

Lasting
neuropathological changes in rat brain after intermittent neonatal
administration of thimerosal.Folia
Neuropathol. 2010;48(4):258-69. Olczak M, Duszczyk M,
Mierzejewski P, Wierzba-Bobrowicz T, Majewska MD.Department
of Pharmacology and Physiology of the Nervous System, Institute of
Psychiatry and Neurology, ul. Sobieskiego 9, Warsaw,
Poland.AbstractThimerosal,
an organomercurial added as a preservative to some vaccines, is a
suspected iatrogenic factor, possibly contributing to paediatric
neurodevelopmental disorders including autism. We examined the
effects of early postnatal administration of thimerosal (four i.m.
injections, 12 or 240 μg THIM-Hg/kg, on postnatal days 7, 9, 11 and
15) on brain pathology in Wistar rats. Numerous neuropathological
changes were observed in young adult rats which were treated
postnatally with thimerosal. They included: ischaemic degeneration
of neurons and "dark" neurons in the prefrontal and
temporal cortex, the hippocampus and the cerebellum, pathological
changes of the blood vessels in the temporal cortex, diminished
synaptophysin reaction in the hippocampus, atrophy of astroglia in
the hippocampus and cerebellum, and positive caspase-3 reaction in
Bergmann astroglia. These
findings document neurotoxic effects of thimerosal, at doses
equivalent to those used in infant vaccines or higher, in developing
rat brain, suggesting likely involvement of this mercurial in
neurodevelopmental disorders.

Persistent
behavioral impairments and alterations of brain dopamine system
after early postnatal administration of thimerosal in rats.Behav
Brain Res.2011
Sep 30;223(1):107-18. doi: 10.1016/j.bbr.2011.04.026. Epub 2011 Apr
28.Olczak
M,Duszczyk
M,Mierzejewski
P,Meyza
K,Majewska
MD.
Department of Pharmacology and Physiology of the Nervous System,
Institute of Psychiatry and Neurology, 02-957 Warsaw,
Poland.AbstractThe
neurotoxic organomercurial thimerosal (THIM), used for decades as
vaccine preservative, is a suspected factor in the pathogenesis of
some neurodevelopmental disorders. Previously we showed that
neonatal administration of THIM at doses equivalent to those used in
infant vaccines or higher, causes lasting alterations in the brain
opioid system in rats. Here we investigated neonatal treatment with
THIM (at doses 12, 240, 1440 and 3000 μg Hg/kg) on behaviors, which
are characteristically altered in autism, such as locomotor
activity, anxiety, social interactions, spatial learning, and on the
brain dopaminergic system in Wistar rats of both sexes. Adult male
and female rats, which were exposed to the entire range of THIM
doses during the early postnatal life, manifested impairments of
locomotor activity and increased anxiety/neophobia in the open field
test. In animals of both sexes treated with the highest THIM dose,
the frequency of prosocial interactions was reduced, while the
frequency of asocial/antisocial interactions was increased in males,
but decreased in females. Neonatal THIM treatment did not
significantly affect spatial learning and memory. THIM-exposed rats
also manifested reduced haloperidol-induced catalepsy, accompanied
by a marked decline in the density of striatal D₂
receptors, measured by immunohistochemical staining, suggesting
alterations to the brain dopaminergic system. Males were more
sensitive than females to some neurodisruptive/neurotoxic actions of
THIM. These
data document that early postnatal THIM administration causes
lasting neurobehavioral impairments and neurochemical alterations in
the brain, dependent on dose and sex. If similar changes occur in
THIM/mercurial-exposed children, they could contribute do
neurodevelopmental disorders.

B-Lymphocytes
from a Population of Children with Autism Spectrum Disorder and
Their Unaffected Siblings Exhibit Hypersensitivity to ThimerosalJ
Toxicol. 2013;2013:801517. Epub 2013 Jun 9.Sharpe
MA, Gist TL, Baskin DS.Department
of Neurosurgery, The Methodist Neurological Institute, Houston,
TX.AbstractThe
role of thimerosal containing vaccines in the development of autism
spectrum disorder (ASD) has been an area of intense debate, as has
the presence of mercury dental amalgams and fish ingestion by
pregnant mothers. We studied the effects of thimerosal on cell
proliferation and mitochondrial function from B-lymphocytes taken
from individuals with autism, their nonautistic twins, and their
nontwin siblings. Eleven families were examined and compared to
matched controls. B-cells were grown with increasing levels of
thimerosal, and various assays (LDH, XTT, DCFH, etc.) were performed
to examine the effects on cellular proliferation and mitochondrial
function. A subpopulation of eight individuals (4 ASD, 2 twins, and
2 siblings) from four of the families showed thimerosal
hypersensitivity, whereas none of the control individuals displayed
this response. The thimerosal concentration required to inhibit cell
proliferation in these individuals was only 40% of controls. Cells
hypersensitive to thimerosal also had higher levels of oxidative
stress markers, protein carbonyls, and oxidant generation. This
suggests certain individuals with a mild mitochondrial defect may be
highly susceptible to mitochondrial specific toxins like the vaccine
preservative thimerosal.

AbstractThimerosal generates ethylmercury in
aqueous solution and is widely used as preservative. We have
investigated the toxicology of Thimerosal in normal human astrocytes,
paying particular attention to mitochondrial function and the
generation of specific oxidants. We
find that ethylmercury not only inhibits mitochondrial respiration
leading to a drop in the steady state membrane potential, but also
concurrent with these phenomena increases the formation of
superoxide, hydrogen peroxide, and Fenton/Haber-Weiss generated
hydroxyl radical. These oxidants increase the levels of cellular
aldehyde/ketones. Additionally, we find a five-fold increase in the
levels of oxidant damaged mitochondrial DNA bases and increases in
the levels of mtDNA nicks and blunt-ended breaks. Highly damaged
mitochondria are characterized by having very low membrane
potentials, increased superoxide/hydrogen peroxide production, and
extensively damaged mtDNA and proteins. These mitochondria appear to
have undergone a permeability transition, an observation supported by
the five-fold increase in Caspase-3 activity observed after
Thimerosal treatment.

Oxidative
stress increases serum thioredoxin (TRX), a redox-regulating protein
with antioxidant activity recognized as an oxidative-stress marker.
The aim of this study was to assess the clinical significance of
serum TRX levels in Autism spectrum disorders (ASD).

METHODS:

Eighty
patients diagnosed with ASD and 100 sex and age matched typically
developing children were assessed for serum TRX content at admission.
TRX were assayed with solid-phase sandwich ELISA, and severity of ASD
was evaluated with the Childhood Autism Rating Scale (CARS) Score.

RESULTS:

The
results indicated that the median serum TRX levels were significantly
(P<0.0001) higher in children with ASD as compared to typically
developing children [17.9(IQR: 10.7-25.8)ng/ml and 5.5(3.6-9.2)ng/ml,
respectively]. Levels of TRX increased with increasing severity of
ASD as defined by the CARS score. After adjusting for all other
possible covariates, TRX still was an independent diagnosis marker of
ASD with an adjusted OR of 1.454 (95% CI, 1.232-1.892; P<0.0001).
Based on the receiver operating characteristic (ROC) curve, the
optimal cut-off value of serum TRX levels as an indicator for
auxiliary diagnosis of autism was projected to be 10.6ng/ml. Further,
we found that an increased diagnosis of ASD was associated with TRX
levels ≥10.6ng/ml (adjusted OR 15.31, 95% CI: 7.36-31.85) after
adjusting for possible confounders.

CONCLUSIONS:

Our
study demonstrated that serum TRX levels were associated with ASD,
and elevated levels could be considered as a novel, independent
diagnosis indicator of ASD.

Mercury
toxicity mediated by different forms of mercury is a major health
problem; however, the molecular mechanisms underlying toxicity remain
elusive. We analyzed the effects of mercuric chloride (HgCl(2)) and
monomethylmercury (MeHg) on the proteins of the mammalian thioredoxin
system, thioredoxin reductase (TrxR) and thioredoxin (Trx), and of
the glutaredoxin system, glutathione reductase (GR) and glutaredoxin
(Grx). HgCl(2) and MeHg inhibited recombinant rat TrxR with IC(50)
values of 7.2 and 19.7 nm, respectively. Fully reduced human Trx1
bound mercury and lost all five free thiols and activity after
incubation with HgCl(2) or MeHg, but only HgCl(2) generated dimers.
Mass spectra analysis demonstrated binding of 2.5 mol of Hg(2+) and 5
mol of MeHg(+)/mol of Trx1 with the very strong Hg(2+) complexes
involving active site and structural disulfides. Inhibition of both
TrxR and Trx activity was observed in HeLa and HEK 293 cells treated
with HgCl(2) or MeHg. GR was inhibited by HgCl(2) and MeHg in vitro,
but no decrease in GR activity was detected in cell extracts treated
with mercurials. Human Grx1 showed similar reactivity as Trx1 with
both mercurial compounds, with the loss of all free thiols and Grx
dimerization in the presence of HgCl(2), but no inhibition of Grx
activity was observed in lysates of HeLa cells exposed to mercury.
Overall, mercury inhibition was selective toward the thioredoxin
system. In particular, the remarkable potency of the mercury
compounds to bind to the selenol-thiol in the active site of TrxR
should be a major molecular mechanism of mercury toxicity.

Mercury
toxicity is a highly interesting topic in biomedicine due to the
severe endpoints and treatment limitations. Selenite serves as an
antagonist of mercury toxicity, but the molecular mechanism of
detoxification is not clear. Inhibition of the selenoenzyme
thioredoxin reductase (TrxR) is a suggested mechanism of toxicity.
Here, we demonstrated enhanced inhibition of activity by inorganic
and organic mercury compounds in NADPH-reduced TrxR, consistent with
binding of mercury also to the active site selenolthiol. On treatment
with 5 μM selenite and NADPH, TrxR inactivated by HgCl(2) displayed
almost full recovery of activity. Structural analysis indicated that
mercury was complexed with TrxR, but enzyme-generated selenide
removed mercury as mercury selenide, regenerating the active site
selenocysteine and cysteine residues required for activity. The
antagonistic effects on TrxR inhibition were extended to endogenous
antioxidants, such as GSH, and clinically used exogenous chelating
agents BAL, DMPS, DMSA, and α-lipoic acid. Consistent with the in
vitro results, recovery of TrxR activity and cell viability by
selenite was observed in HgCl(2)-treated HEK 293 cells. These results
stress the role of TrxR as a target of mercurials and provide the
mechanism of selenite as a detoxification agent for mercury
poisoning.

Serological
association of measles virus and human herpesvirus-6 with brain
autoantibodies in autism.Clin
Immunol Immunopathol.1998
Oct;89(1):105-8.Singh
VK,Lin
SX,Yang
VC.
College of Pharmacy, University of Michigan, Ann Arbor, Michigan,
48109-1065, USA.AbstractConsidering
an autoimmunity and autism connection, brain autoantibodies to
myelin basic protein (anti-MBP) and neuron-axon filament protein
(anti-NAFP) have been found in autistic children. In this current
study, we examined associations between virus serology and
autoantibody by simultaneous analysis of measles virus antibody
(measles-IgG), human herpesvirus-6 antibody (HHV-6-IgG), anti-MBP,
and anti-NAFP. We found that measles-IgG and HHV-6-IgG titers were
moderately higher in autistic children but they did not
significantly differ from normal controls. Moreover, we found that a
vast majority of virus serology-positive autistic sera was also
positive for brain autoantibody: (i) 90% of measles-IgG-positive
autistic sera was also positive for anti-MBP; (ii) 73% of
measles-IgG-positive autistic sera was also positive for anti-NAFP;
(iii) 84% of HHV-6-IgG-positive autistic sera was also positive for
anti-MBP; and (iv) 72% of HHV-6-IgG-positive autistic sera was also
positive for anti-NAFP. This
study is the first to report an association between virus serology
and brain autoantibody in autism; it supports the hypothesis that a
virus-induced autoimmune response may play a causal role in
autism.

Metabolic
biomarkers of increased oxidative stress and impaired methylation
capacity in children with autismAmerican
Journal of Clinical Nutrition, Vol. 80, No. 6, 1611-1617, December
2004Department
of Pediatrics, University of Arkansas for Medical Sciences, and the
Arkansas Children's Hospital Research
InstituteAbstractBackground:
Autism is a complex neurodevelopmental disorder that usually
presents in early childhood and that is thought to be influenced by
genetic and environmental factors. Although abnormal metabolism of
methionine and homocysteine has been associated with other
neurologic diseases, these pathways have not been evaluated in
persons with autism.Objective:
The purpose of this study was to evaluate plasma concentrations of
metabolites in the methionine transmethylation and transsulfuration
pathways in children diagnosed with autism.Design:
Plasma concentrations of methionine, S-adenosylmethionine (SAM),
S-adenosylhomocysteine (SAH), adenosine, homocysteine,
cystathionine, cysteine, and oxidized and reduced glutathione were
measured in 20 children with autism and in 33 control children. On
the basis of the abnormal metabolic profile, a targeted nutritional
intervention trial with folinic acid, betaine, and methylcobalamin
was initiated in a subset of the autistic children.Results:
Relative to the control children, the children with autism had
significantly lower baseline plasma concentrations of methionine,
SAM, homocysteine, cystathionine, cysteine, and total glutathione
and significantly higher concentrations of SAH, adenosine, and
oxidized glutathione. This metabolic profile is consistent with
impaired capacity for methylation (significantly lower ratio of SAM
to SAH) and increased oxidative stress (significantly lower redox
ratio of reduced glutathione to oxidized glutathione) in children
with autism. The intervention trial was effective in normalizing the
metabolic imbalance in the autistic children.Conclusions:
An
increased vulnerability to oxidative stress and a decreased capacity
for methylation may contribute to the development and clinical
manifestation of autism.

Porphyrinuria
in childhood autistic disorder: Implications for environmental
toxicityToxicology
and Applied Pharmacology, 2006Robert
Natafa, Corinne Skorupkab, Lorene Ametb, Alain Lama, Anthea
Springbettc and Richard Lathed, aLaboratoire Philippe Auguste,
Paris, France, Association ARIANE, Clichy, France, Department of
Statistics, Roslin Institute, Roslin, UK, Pieta Research,This
new study from France utilizes a new and sophisticated measurement
for environmental toxicity by assessing porphyrin levels in autistic
children. It provides clear and unequivocal evidence that children
with autism spectrum disorders are more toxic than their
neurotypical peers.Excerpt:
"Coproporphyrin levels were elevated in children with autistic
disorder relative to control groups...the elevation was significant.
These data implicate environmental toxicity in childhood autistic
disorder."AbstractTo
address a possible environmental contribution to autism, we carried
out a retrospective study on urinary porphyrin levels, a biomarker
of environmental toxicity, in 269 children with neurodevelopmental
and related disorders referred to a Paris clinic (2002–2004),
including 106 with autistic disorder. Urinary porphyrin levels
determined by high-performance liquid chromatography were compared
between diagnostic groups including internal and external control
groups. Coproporphyrin levels were elevated in children with
autistic disorder relative to control groups. Elevation was
maintained on normalization for age or to a control heme pathway
metabolite (uroporphyrin) in the same samples. The elevation was
significant (P < 0.001). Porphyrin levels were unchanged in
Asperger's disorder, distinguishing it from autistic disorder. The
atypical molecule precoproporphyrin, a specific indicator of heavy
metal toxicity, was also elevated in autistic disorder (P <
0.001) but not significantly in Asperger's. A subgroup with autistic
disorder was treated with oral dimercaptosuccinic acid (DMSA) with a
view to heavy metal removal. Following DMSA there was a significant
(P = 0.002) drop in urinary porphyrin excretion. These
data implicate environmental toxicity in childhood autistic
disorder.

Uncoupling
of ATP-mediated Calcium Signaling and Dysregulated IL-6 Secretion in
Dendritic Cells by Nanomolar ThimerosalEnvironmental
Health Perspectives, July 2006.Samuel
R. Goth, Ruth A. Chu Jeffrey P. GreggThis
study demonstrates that very low-levels of Thimerosal can contribute
to immune system disregulation.Excerpt:
"Our findings that DCs primarily express the RyR1 channel
complex and that this complex is uncoupled by very low levels of THI
with dysregulated IL-6 secretion raise intriguing questions about a
molecular basis for immune dyregulation and the possible role of the
RyR1 complex in genetic susceptibility of the immune system to
mercury."

Comparison
of Blood and Brain Mercury Levels in Infant Monkeys Exposed to
Methylmercury or Vaccines Containing ThimerosalEnvironmental
Health Perspectives, Aug 2005.Thomas
Burbacher, PhD [University of Washington].This
study demonstrates clearly and unequivocally that ethyl mercury, the
kind of mercury found in vaccines, not only ends up in the brain,
but leaves double the amount of inorganic mercury as methyl mercury,
the kind of mercury found in fish. This work is groundbreaking
because little is known about ethyl mercury, and many health
authorities have asserted that the mercury found in vaccines is the
"safe kind." This study also delivers a strong rebuke of
the Institute of Medicine's recommendation in 2004 to no longer
pursue the mercury-autism connection.Excerpt:
"A recently published IOM review (IOM 2004) appears to have
abandoned the earlier recommendation [of studying mercury and
autism] as well as back away from the American Academy of Pediatrics
goal [of removing mercury from vaccines]. This approach is difficult
to understand, given our current limited knowledge of the
toxicokinetics and developmental neurotoxicity of thimerosal, a
compound that has been (and will continue to be) injected in
millions of newborns and infants."

AbstractThe
number of neurons, astrocytes, reactive glia, oligodendrocytes,
endothelia, and pericytes in the cortex of the calcarine sulcus of
adult female Macaca fascicularis following long-term subclinical
exposure to methyl mercury (MeHg) and mercuric chloride (inorganic
mercury; IHg) has been estimated by use of the optical volume
fractionator stereology technique. Four groups of monkeys were
exposed to MeHg (50 micrograms Hg/kg body wt/day) by mouth for 6,
12, 18, and 12 months followed by 6 months without exposure
(clearance group). A fifth group of monkeys was administered IHg (as
HgCl2; 200 micrograms Hg/kg body wt/day) by constant rate
intravenous infusion via an indwelling catheter for 3 months.
Reactive glia showed a significant increase in number for every
treatment group, increasing 72% in the 6-month, 152% in the
12-month, and 120% in the 18-month MeHg exposed groups, and the
number of reactive glia in the clearance group remained elevated
(89%). The IHg exposed group showed a 165% increase in the number of
reactive glia. The IHg exposed group and the clearance group had low
levels of MeHg present within the tissue; however, the level of IHg
was elevated in both groups. These
results suggest that the IHg may be responsible for the increase in
reactive glia.
All other cell types, including the neurons, showed no significant
change in number at the prescribed exposure level and durations. The
identities of the reactive glial cells and the implications for the
long-term function and survivability of the neurons due to changes
in the glial population following subclinical long-term exposure to
mercury are discussed.

Neuroglial
Activation and Neuroinflammation in the Brain of Patients with
AutismAnnals
of Neurology, Feb 2005.Diana
L. Vargas, MD, Johns Hopkins University.AbstractAutism
is a neurodevelopmental disorder characterized by impaired
communication and social interaction and may be accompanied by
mental retardation and epilepsy. Its cause remains unknown, despite
evidence that genetic, environmental, and immunological factors may
play a role in its pathogenesis. To investigate whether
immune-mediated mechanisms are involved in the pathogenesis of
autism, we used immunocytochemistry, cytokine protein arrays, and
enzyme-linked immunosorbent assays to study brain tissues and
cerebrospinal fluid (CSF) from autistic patients and determined the
magnitude of neuroglial and inflammatory reactions and their
cytokine expression profiles. Brain tissues from cerebellum,
midfrontal, and cingulate gyrus obtained at autopsy from 11 patients
with autism were used for morphological studies. Fresh-frozen
tissues available from seven patients and CSF from six living
autistic patients were used for cytokine protein profiling. We
demonstrate an active neuroinflammatory process in the cerebral
cortex, white matter, and notably in cerebellum of autistic
patients. Immunocytochemical studies showed marked activation of
microglia and astroglia, and cytokine profiling indicated that
macrophage chemoattractant protein (MCP)-1 and tumor growth
factor-beta1, derived from neuroglia, were the most prevalent
cytokines in brain tissues. CSF showed a unique proinflammatory
profile of cytokines, including a marked increase in MCP-1. Our
findings indicate that innate neuroimmune reactions play a
pathogenic role in an undefined proportion of autistic patients,
suggesting that future therapies might involve modifying neuroglial
responses in the brain.Excerpt:
"Because
this neuroinflammatory process appears to be associated with an
ongoing and chronic mechanism of CNS dysfunction, potential
therapeutic interventions should focus on the control of its
detrimental effects and thereby eventually modify the clinical
course of autism."

Autism:
A Brain Disorder, or A Disorder That Affects the Brain?Clinical
Neuropsychiatry, 2005Martha
R. Herbert M.D., Ph.D., Harvard UniversityAutism
is defined behaviorally, as a syndrome of abnormalities involving
language, social reciprocity and hyperfocus or reduced behavioral
flexibility. It is clearly heterogeneous, and it can be accompanied
by unusual talents as well as by impairments, but its underlying
biological and genetic basis in unknown. Autism has been modeled as
a brain-based, strongly genetic disorder, but emerging findings and
hypotheses support a broader model of the condition as a genetically
influenced and systemic. These include imaging, neuropathology and
psychological evidence of pervasive (and not just specific) brain
and phenotypic features; postnatal evolution and chronic persistence
of brain, behavior and tissue changes (e.g. inflammation) and
physical illness symptomatology (e.g. gastrointestinal, immune,
recurrent infection); overlap with other disorders; and reports of
rate increases and improvement or recovery that support a role for
modulation of the condition by environmental factors (e.g.
exacerbation or triggering by toxins, infectious agents, or others
stressors, or improvement by treatment). Modeling autism more
broadly encompasses previous work, but also encourages the expansion
of research and treatment to include intermediary domains of
molecular and cellular mechanisms, as well as chronic tissue,
metabolic and somatic changes previously addressed only to a limited
degree. The heterogeneous biologies underlying autism may
conceivably converge onto the autism profile via multiple mechanisms
on the one hand and processing and connectivity abnormalities on the
other may illuminate relevant final common pathways and contribute
to focusing on the search for treatment targets in this biologically
and etiologically heterogeneous behavioral syndrome.

Activation
of Methionine Synthase by Insulin-like Growth Factor-1 and Dopamine:
a Target for Neurodevelopmental Toxins and ThimerosalMol
Psychiatry. 2004 Apr;9(4):358-70.Waly
M, Olteanu H, Banerjee R, Choi SW, Mason JB, Parker BS, Sukumar S,
Shim S, Sharma A, Benzecry JM, Power-Charnitsky VA, Deth RC.
Department of Pharmaceutical Sciences, Northeastern University,
Boston, MA AbstractMethylation
events play a critical role in the ability of growth factors to
promote normal development. Neurodevelopmental toxins, such as
ethanol and heavy metals, interrupt growth factor signaling, raising
the possibility that they might exert adverse effects on
methylation. We found that insulin-like growth factor-1 (IGF-1)- and
dopamine-stimulated methionine synthase (MS) activity and
folate-dependent methylation of phospholipids in SH-SY5Y human
neuroblastoma cells, via a PI3-kinase- and MAP-kinase-dependent
mechanism. The stimulation of this pathway increased DNA
methylation, while its inhibition increased methylation-sensitive
gene expression. Ethanol potently interfered with IGF-1 activation
of MS and blocked its effect on DNA methylation, whereas it did not
inhibit the effects of dopamine. Metal ions potently affected IGF-1
and dopamine-stimulated MS activity, as well as folate-dependent
phospholipid methylation: Cu(2+) promoted enzyme activity and
methylation, while Cu(+), Pb(2+), Hg(2+) and Al(3+) were inhibitory.
The ethylmercury-containing preservative thimerosal inhibited both
IGF-1- and dopamine-stimulated methylation with an IC(50) of 1 nM
and eliminated MS activity. Our findings outline a novel growth
factor signaling pathway that regulates MS activity and thereby
modulates methylation reactions, including DNA methylation. The
potent inhibition of this pathway by ethanol, lead, mercury,
aluminum and thimerosal suggests that it may be an important target
of neurodevelopmental toxins.

AbstractObjective
To validate parental report of autistic regression using behavioral
data coded from home videotapes of children with autism spectrum
disorder (ASD) vs typical development taken at 12 and 24 months of
age.Design
Home videotapes of 56 children’s first and second birthday parties
were collected from parents of young children with ASD with and
without a reported history of regression and typically developing
children. Child behaviors were coded by raters blind to child
diagnosis and regression history. A parent interview that elicited
information about parents’ recall of early symptoms from birth was
also administered.Setting
Participants were recruited from a multidisciplinary study of autism
conducted at a major university.Participants
Fifteen children with ASD with a history of regression, 21 children
with ASD with early-onset autism, and 20 typically developing
children and their parents participated.Main
Outcome Measures Observations of children’s communicative, social,
affective, repetitive behaviors, and toy play coded from videotapes
of the toddlers’ first and second birthday parties.Results
Analyses revealed that infants with ASD with regression show similar
use of joint attention and more frequent use of words and babble
compared with typical infants at 12 months of age. In contrast,
infants with ASD with early onset of symptoms and no regression
displayed fewer joint attention and communicative behaviors at 12
months of age. By 24 months of age, both groups of toddlers with ASD
displayed fewer instances of word use, vocalizations, declarative
pointing, social gaze, and orienting to name as compared with
typically developing 24-month-olds.Parent
interview data suggested that some children with regression
displayed difficulties in regulatory behavior before the regression
occurred.Conclusion
This
study validates the existence of early autistic regression.

AbstractThe
question of what is leading to the apparent increase in autism is of
great importance. Like the link between aspirin and heart attack,
even a small effect can have major health implications. If there is
any link between autism and mercury, it is absolutely crucial that
the first reports of the question are not falsely stating that no
link occurs. We
have reanalyzed the data set originally reported by Ip et al. in
2004 and have found that the original p value was in error and that
a significant relation does exist between the blood levels of
mercury and diagnosis of an autism spectrum disorder. Moreover, the
hair sample analysis results offer some support for the idea that
persons with autism may be less efficient and more variable at
eliminating mercury from the blood.

Empirical
Data Confirm Autism Symptoms Related to Aluminum and Acetaminophen
ExposureEntropy,
November 7, 2012Stephanie
Seneff, Robert M. Davidson and Jingjing LiuComputer
Science and Artificial Intelligence Laboratory, Massachusetts
Institute of Technology, Cambridge, MA 02139, USA, Internal
Medicine Group Practice, PhyNet, Inc., Longview, TX 75604,
USAAbstractAutism
is a condition characterized by impaired cognitive and social
skills, associated with compromised immune function. The incidence
is alarmingly on the rise, and environmental factors are
increasingly suspected to play a role. This paper investigates word
frequency patterns in the U.S. CDC Vaccine Adverse Events Reporting
System (VAERS) database. Our results provide strong evidence
supporting a link between autism and the aluminum in vaccines. A
literature review showing toxicity of aluminum in human physiology
offers further support. Mentions of autism in VAERS increased
steadily at the end of the last century, during a period when
mercury was being phased out, while aluminum adjuvant burden was
being increased. Using standard log-likelihood ratio techniques, we
identify several signs and symptoms that are significantly more
prevalent in vaccine reports after 2000, including cellulitis,
seizure, depression, fatigue, pain and death, which are also
significantly associated with aluminum-containing vaccines.We
propose that children with the autism diagnosis are especially
vulnerable to toxic metals such as aluminum and mercury due to
insufficient serum sulfate and glutathione.A
strong correlation between autism and the MMR (Measles, Mumps,
Rubella) vaccine is also observed, which may be partially explained
via an increased sensitivity to acetaminophen administered to
control fever.

Developmental
Regression and Mitochondrial Dysfunction in a Child With AutismJ
Child Neurol. 2006 Feb;21(2):170-2.Jon
S. Poling, MD, PhD, Department of Neurology and NeurosurgeryJohns
Hopkins HospitalAbstractAutistic
spectrum disorders can be associated with mitochondrial dysfunction.
We present a singleton case of developmental regression and
oxidative phosphorylation disorder in a 19-month-old girl. Subtle
abnormalities in the serum creatine kinase level, aspartate
aminotransferase, and serum bicarbonate led us to perform a muscle
biopsy, which showed type I myofiber atrophy, increased lipid
content, and reduced cytochrome c oxidase activity. There were
marked reductions in enzymatic activities for complex I and III.
Complex IV (cytochrome c oxidase) activity was near the 5%
confidence level. To determine the frequency of routine laboratory
abnormalities in similar patients, we performed a retrospective
study including 159 patients with autism (Diagnostic and Statistical
Manual of Mental Disorders-IV and Childhood Autism Rating Scale) not
previously diagnosed with metabolic disorders and 94 age-matched
controls with other neurologic disorders. Aspartate aminotransferase
was elevated in 38% of patients with autism compared with 15% of
controls (P <.0001). The serum creatine kinase level also was
abnormally elevated in 22 (47%) of 47 patients with autism. These
data suggest that further metabolic evaluation is indicated in
autistic patients and that defects of oxidative phosphorylation
might be prevalent.

Excerpt:
"Children
who have (mitochondrial-related) dysfunctional cellular energy
metabolism might be more prone to undergo autistic regression
between 18 and 30 months of age if they also have infections or
immunizations at the same time.”

Abstract
It
has been suggested that oxidative stress and/or mercury compounds
play an important role in the pathophysiology of autism. This study
compared for the first time the cerebellar levels of the oxidative
stress marker 3-nitrotyrosine (3-NT), mercury (Hg) and the
antioxidant selenium (Se) levels between control and autistic
subjects. Tissue homogenates were prepared in the presence of
protease inhibitors from the frozen cerebellar tissue of control
(n=10; mean age, 15.5 years; mean PMI, 15.5 hours) and autistic
(n=9; mean age 12.1 years; mean PMI, 19.3 hours) subjects. The
concentration of cerebellar 3-NT, determined by ELISA, in controls
ranged from 13.69 to 49.04 pmol g-1of
tissue; the concentration of 3-NT in autistic cases ranged from 3.91
to 333.03 pmol g-1of
tissue. Mean cerebellar 3-NT was elevated in autism by 68.9% and the
increase was statistically significant (p=0.045). Cerebellar Hg,
measured by atomic absorption spectrometry ranged from 0.9 to 35
pmol g-1tissue
in controls (n=10) and from 3.2 to 80.7 pmol g-1tissue
in autistic cases (n=9); the 68.2% increase in cerebellar Hg was not
statistically significant. However, there was a positive correlation
between cerebellar 3-NT and Hg levels (r=0.7961, p=0.0001). A small
decrease in cerebellar Se levels in autism, measured by atomic
absorption spectroscopy, was not statistically significant but was
accompanied by a 42.9% reduction in the molar ratio of Se to Hg in
the autistic cerebellum. While preliminary, the results of the
present study add elevated oxidative stress markers in brain to the
growing body of data reflecting greater oxidative stress in
autism.

Excerpt: The
preliminary data suggest a need for more extensive studies of
oxidative stress, its relationship to the environmental factors and
its possible attenuation by antioxidants in autism.”

Large
Brains in Autism: The Challenge of Pervasive
AbnormalityNeuroscientist.
2005 Oct;11(5):417-40.Herbert
MR., Harvard UniversityPediatric
Neurology, Center for Morphometric Analysis, Massachusetts General
Hospital, Charleston, MA AbstractThe
most replicated finding in autism neuroanatomy-a tendency to
unusually large brains-has seemed paradoxical in relation to the
specificity of the abnormalities in three behavioral domains that
define autism. We now know a range of things about this phenomenon,
including that brains in autism have a growth spurt shortly after
birth and then slow in growth a few short years afterward, that only
younger but not older brains are larger in autism than in controls,
that white matter contributes disproportionately to this volume
increase and in a nonuniform pattern suggesting postnatal pathology,
that functional connectivity among regions of autistic brains is
diminished, and that neuroinflammation (including microgliosis and
astrogliosis) appears to be present in autistic brain tissue from
childhood through adulthood. Alongside these pervasive brain tissue
and functional abnormalities, there have arisen theories of
pervasive or widespread neural information processing or signal
coordination abnormalities (such as weak central coherence, impaired
complex processing, and underconnectivity), which are argued to
underlie the specific observable behavioral features of autism. This
convergence of findings and models suggests that a systems- and
chronic disease-based reformulation of function and pathophysiology
in autism needs to be considered, and it opens the possibility for
new treatment targets..Excerpt:
"Oxidative
stress, brain inflammation, and microgliosis have been much
documented in association with toxic exposures including various
heavy metals...the awareness that the brain as well as medical
conditions of children with autism may be conditioned by chronic
biomedical abnormalities such as inflammation opens the possibility
that meaningful biomedical interventions may be possible well past
the window of maximal neuroplasticity in early childhood because the
basis for assuming that all deficits can be attributed to fixed
early developmental alterations in neural architecture has now been
undermined."

Evidence
of Toxicity, Oxidative Stress, and Neuronal Insult in AutismJ
Toxicol Environ Health B Crit Rev. 2006 Nov-Dec;9(6):485-99.Kern
JK, Jones AM.Department
of Psychiatry, University of Texas Southwestern Medical Center at
Dallas, Dallas, Texas AbstractAccording
to the Autism Society of America, autism is now considered to be an
epidemic. The increase in the rate of autism revealed by
epidemiological studies and government reports implicates the
importance of external or environmental factors that may be
changing. This article discusses the evidence for the case that some
children with autism may become autistic from neuronal cell death or
brain damage sometime after birth as result of insult; and addresses
the hypotheses that toxicity and oxidative stress may be a cause of
neuronal insult in autism. The article first describes the Purkinje
cell loss found in autism, Purkinje cell physiology and
vulnerability, and the evidence for postnatal cell loss. Second, the
article describes the increased brain volume in autism and how it
may be related to the Purkinje cell loss. Third, the evidence for
toxicity and oxidative stress is covered and the possible
involvement of glutathione is discussed. Finally, the article
discusses what may be happening over the course of development and
the multiple factors that may interplay and make these children more
vulnerable to toxicity, oxidative stress, and neuronal insult.

Oxidative
Stress in AutismPathophysiology.
2006 Aug;13(3):171-81. Epub 2006 Jun 12.Chauhan
A, Chauhan V.NYS
Institute for Basic Research in Developmental Disabilities, 1050
Forest Hill Road, Staten Island, NY AbstractAutism
is a severe developmental disorder with poorly understood etiology.
Oxidative stress in autism has been studied at the membrane level
and also by measuring products of lipid peroxidation, detoxifying
agents (such as glutathione), and antioxidants involved in the
defense system against reactive oxygen species (ROS). Lipid
peroxidation markers are elevated in autism, indicating that
oxidative stress is increased in this disease. Levels of major
antioxidant serum proteins, namely transferrin (iron-binding
protein) and ceruloplasmin (copper-binding protein), are decreased
in children with autism. There is a positive correlation between
reduced levels of these proteins and loss of previously acquired
language skills in children with autism. The alterations in
ceruloplasmin and transferrin levels may lead to abnormal iron and
copper metabolism in autism. The membrane phospholipids, the prime
target of ROS, are also altered in autism. The levels of
phosphatidylethanolamine (PE) are decreased, and phosphatidylserine
(PS) levels are increased in the erythrocyte membrane of children
with autism as compared to their unaffected siblings. Several
studies have suggested alterations in the activities of antioxidant
enzymes such as superoxide dismutase, glutathione peroxidase, and
catalase in autism. Additionally, altered glutathione levels and
homocysteine/methionine metabolism, increased inflammation,
excitotoxicity, as well as mitochondrial and immune dysfunction have
been suggested in autism. Furthermore, environmental and genetic
factors may increase vulnerability to oxidative stress in autism.
Taken together, these studies suggest increased oxidative stress in
autism that may contribute to the development of this disease. A
mechanism linking oxidative stress with membrane lipid
abnormalities, inflammation, aberrant immune response, impaired
energy metabolism and excitotoxicity, leading to clinical symptoms
and pathogenesis of autism is proposed.Excerpt:
"Upon
completion of this article, participants should be able to: 1. Be
aware of laboratory and clinical evidence of greater oxidative
stress in autism. 2. Understand how gut, brain, nutritional, and
toxic status in autism are consistent with greater oxidative stress.
3. Describe how anti-oxidant nutrients are used in the contemporary
treatment of autism."

Thimerosal
Neurotoxicity is Associated with Glutathione Depletion: Protection
with Glutathione PrecursorsNeurotoxicology.
2005 Jan;26(1):1-8.James
SJ, Slikker W 3rd, Melnyk S, New E, Pogribna M, Jernigan
S.Department
of Pediatrics, University of Arkansas for Medical Sciences and
Arkansas Children's Hospital Research Institute, Little Rock, AR
AbstractThimerosol
is an antiseptic containing 49.5% ethyl mercury that has been used
for years as a preservative in many infant vaccines and in flu
vaccines. Environmental methyl mercury has been shown to be highly
neurotoxic, especially to the developing brain. Because mercury has
a high affinity for thiol (sulfhydryl (-SH)) groups, the
thiol-containing antioxidant, glutathione (GSH), provides the major
intracellular defense against mercury-induced neurotoxicity.
Cultured neuroblastoma cells were found to have lower levels of GSH
and increased sensitivity to thimerosol toxicity compared to
glioblastoma cells that have higher basal levels of intracellular
GSH. Thimerosal-induced
cytotoxicity was associated with depletion of intracellular GSH in
both cell lines.
Pretreatment with 100 microM glutathione ethyl ester or
N-acetylcysteine (NAC), but not methionine, resulted in a
significant increase in intracellular GSH in both cell types.
Further, pretreatment of the cells with glutathione ethyl ester or
NAC prevented cytotoxicity with exposure to 15 microM Thimerosal.
Although Thimerosal has been recently removed from most children's
vaccines, it is still present in flu vaccines given to pregnant
women, the elderly, and to children in developing countries. The
potential protective effect of GSH or NAC against mercury toxicity
warrants further research as possible adjunct therapy to individuals
still receiving Thimerosal-containing vaccinations.

Aluminum
adjuvant linked to gulf war illness induces motor neuron death in
miceNeuromolecular
Med. 2007;9(1):83-100.Petrik
MS, Wong MC, Tabata RC, Garry RF, Shaw CA.Department
of Ophthalmology and Program in Neuroscience, University of British
Columbia, Vancouver, British Columbia, Canada. AbstractGulf
War illness (GWI) affects a significant percentage of veterans of
the 1991 conflict, but its origin remains unknown. Associated with
some cases of GWI are increased incidences of amyotrophic lateral
sclerosis and other neurological disorders. Whereas many
environmental factors have been linked to GWI, the role of the
anthrax vaccine has come under increasing scrutiny. Among the
vaccine's potentially toxic components are the adjuvants aluminum
hydroxide and squalene. To examine whether these compounds might
contribute to neuronal deficits associated with GWI, an animal model
for examining the potential neurological impact of aluminum
hydroxide, squalene, or aluminum hydroxide combined with squalene
was developed. Young, male colony CD-1 mice were injected with the
adjuvants at doses equivalent to those given to US military service
personnel. All mice were subjected to a battery of motor and
cognitive-behavioral tests over a 6-mo period postinjections.
Following sacrifice, central nervous system tissues were examined
using immunohistochemistry for evidence of inflammation and cell
death. Behavioral testing showed motor deficits in the aluminum
treatment group that expressed as a progressive decrease in strength
measured by the wire-mesh hang test (final deficit at 24 wk; about
50%). Significant cognitive deficits in water-maze learning were
observed in the combined aluminum and squalene group (4.3 errors per
trial) compared with the controls (0.2 errors per trial) after 20
wk. Apoptotic neurons were identified in aluminum-injected animals
that showed significantly increased activated caspase-3 labeling in
lumbar spinal cord (255%) and primary motor cortex (192%) compared
with the controls. Aluminum-treated groups also showed significant
motor neuron loss (35%) and increased numbers of astrocytes (350%)
in the lumbar spinal cord. The findings suggest a possible role for
the aluminum adjuvant in some neurological features associated with
GWI and possibly an additional role for the combination of
adjuvants.

Funding: This work was supported in
part by National Institutes of Health awards National Institute of
Child Health and Human Development R21HD065289 (PL), National
Institute of General Medical Sciences T32GM07347 for the Vanderbilt
Medical Scientist Training Program (PG), National Center for
Research Resources TL1RR024978 (PG), and National Center for
Advancing Translational Sciences UL1TR000445 for the Vanderbilt
Institute for Clinical and Translational Research. Additional
support was provided by the Marino Autism Research Institute, the
Pediatric Clinical Research Center at Vanderbilt University, The
Scott Family Foundation, and the Vanderbilt Autism Treatment Network
Site, a program funded by Autism Speaks.

AbstractEtiology is
unknown in the majority of individuals with autism spectrum disorder
(ASD). One strategy to investigate pathogenesis is to stratify this
heterogeneous disorder based on a prominent phenotypic feature that
enriches for homogeneity within population strata. Co-occurring
gastrointestinal dysfunction (GID) characterizes a subset of
children with ASD. Our current objective was to investigate a
potential pathophysiological measure to test the hypothesis that
children with both ASD and GID have a more severe metabolic
dysfunction than children with ASD-only, given that the highly
metabolically active brain and gastrointestinal system may
additively contribute measurable impairment. Plasma levels of
F2t-Isoprostanes (F2-IsoPs), a gold standard biomarker of oxidative
stress, were measured in 87 children in four groups: ASD-GID,
ASD-only, GID-only and Unaffected. F2-IsoP levels were elevated in
all 3 clinical groups compared to the Unaffected group, with the
ASD-GID group significantly elevated above the ASD-only group (mean,
SD in pg/mg: ASD-GID 53.6, 24.4; ASD-only 36.5, 13.3; p = 0.007).
Adjusting for age, sex, and triglyceride levels, F2-IsoP levels
remained significantly different between study groups, with a
moderate effect size of ηp2 = 0.187 (p = 0.001). Elevation
in peripheral oxidative stress is consistent with, and may
contribute to, the more severe functional impairments in the ASD-GID
group. With
unique medical, metabolic, and behavioral features in children with
ASD-GID, the present findings serve as a compelling rationale for
both individualized approaches to clinical care and integrated
studies of biomarker enrichment in ASD subgroups that may better
address the complex etiology of ASD.

University of Texas Health Science
Center, San Antonio Department of Family and Community Medicine,
7703 Floyd Curl Drive, San Antonio, Texas

AbstractThe
association between environmentally released mercury, special
education and autism rates in Texas was investigated using data from
the Texas Education Department and the United States Environmental
Protection Agency. A Poisson regression analysis adjusted for school
district population size, economic and demographic factors was used.
There was a significant increase in the rates of special education
students and autism rates associated with increases in
environmentally released mercury. On average, for each 1,000 lb of
environmentally released mercury, there was a 43% increase in the
rate of special education services and a 61% increase in the rate of
autism. The association between environmentally released mercury and
special education rates were fully mediated by increased autism
rates. This ecological study suggests the need for further research
regarding the association between environmentally released mercury
and developmental disorders such as autism. These results have
implications for policy planning and cost analysis.

AbstractReported rates of autism have increased
sharply in the United States and the United Kingdom. One possible
factor underlying these increases is increased exposure to mercury
through thimerosal-containing vaccines, but vaccine exposures need
to be evaluated in the context of cumulative exposures during
gestation and early infancy. Differential rates of postnatal mercury
elimination may explain why similar gestational and infant exposures
produce variable neurological effects. First baby haircut samples
were obtained from 94 children diagnosed with autism using
Diagnostic and Statistical Manual of Mental Disorders, 4th edition
(DSM IV) criteria and 45 age- and gender-matched controls.
Information on diet, dental amalgam fillings, vaccine history, Rho D
immunoglobulin administration, and autism symptom severity was
collected through a maternal survey questionnaire and clinical
observation. Hair mercury levels in the autistic group were 0.47 ppm
versus 3.63 ppm in controls, a significant difference. The mothers
in the autistic group had significantly higher levels of mercury
exposure through Rho D immunoglobulin injections and amalgam
fillings than control mothers. Within the autistic group, hair
mercury levels varied significantly across mildly, moderately, and
severely autistic children, with mean group levels of 0.79, 0.46,
and 0.21 ppm, respectively. Hair mercury levels among controls were
significantly correlated with the number of the mothers' amalgam
fillings and their fish consumption as well as exposure to mercury
through childhood vaccines, correlations that were absent in the
autistic group. Hair excretion patterns among autistic infants were
significantly reduced relative to control. These data cast doubt on
the efficacy of traditional hair analysis as a measure of total
mercury exposure in a subset of the population. In light of the
biological plausibility of mercury's role in neurodevelopmental
disorders, the present study provides further insight into one
possible mechanism by which early mercury exposures could increase
the risk of autism.

Impairments in social
relatedness and communication, repetitive behaviors, and stereotypic
abnormal movement patterns characterize autism spectrum disorders
(ASDs). It is clear that while genetic factors are important to the
pathogenesis of ASDs, mercury exposure can induce immune, sensory,
neurological, motor, and behavioral dysfunctions similar to traits
defining or associated with ASDs. The Institutional Review Board of
the Institute for Chronic Illnesses (Office for Human Research
Protections, U.S. Department of Health and Human Services, IRB
number IRB00005375) approved the present study. A case series of
nine patients who presented to the Genetic Centers of America for a
genetic/developmental evaluation are discussed. Eight of nine
patients (one patient was found to have an ASD due to Rett's
syndrome) (a) had regressive ASDs; (b) had elevated levels of
androgens; (c) excreted significant amounts of mercury post
chelation challenge; (d) had biochemical evidence of decreased
function in their glutathione pathways; (e) had no known significant
mercury exposure except from Thimerosal-containing
vaccines/Rho(D)-immune globulin preparations; and (f) had alternate
causes for their regressive ASDs ruled out. There was a significant
dose-response relationship between the severity of the regressive
ASDs observed and the total mercury dose children received from
Thimerosal-containing vaccines/Rho (D)-immune globulin preparations.
Based upon differential diagnoses, 8 of 9 patients examined were
exposed to significant mercury from Thimerosal-containing
biologic/vaccine preparations during their fetal/infant
developmental periods, and subsequently, between 12 and 24 mo of
age, these
previously normally developing children suffered mercury toxic
encephalopathies that manifested with clinical symptoms consistent
with regressive ASDs. Evidence for mercury intoxication should be
considered in the differential diagnosis as contributing to some
regressive ASDs.

The
Changing Prevalence of Autism In California Journal
of Autism and Developmental Disorders, April 2003Mark
Blaxill, MBAThis
study helps to refute the supposition made by some researchers that
autism's epidemic may only be due to "diagnostic
substitution".Excerpt:
"They
have suggested that 'diagnostic substitution' accounts for an
apparent increase in the incidence of autism in California that is
not real. This hypothesized substitution is not supported by proper
and detailed analyses of the California data."

Mitochondrial
Energy-Deficient Endophenotype in AutismAmerican
Journal of Biochemistry and Biotechnology 4 (2): 198-207, 2008J.
Jay Gargus and Faiqa ImtiazDepartment
of Physiology and Biophysics and Department of Pediatrics, Section
of Human Genetics, School of Medicine, University of California,
Irvine, Arabian Diagnostics Laboratory, King Faisal Specialist
Hospital and Research CentreAbstract:
While evidence points to a multigenic etiology of most autism, the
pathophysiology of the disorder has yet to be defined and the
underlying genes and biochemical pathways they subserve remain
unknown. Autism is considered to be influenced by a combination of
various genetic, environmental and immunological factors; more
recently, evidence has suggested that increasedvulnerability
to oxidative stress may be involved in the etiology of this
multifactorial disorder.Furthermore,
recent studies have pointed to a subset of autism associated with
the biochemical endophenotype of mitochondrial energy deficiency,
identified as a subtle impairment in fat and carbohydrate oxidation.
This phenotype is similar, but more subtle than those seen in
classic mitochondrial defects. In some cases the beginnings of the
genetic underpinnings of these mitochondrial defects are emerging,
such as mild mitochondrial dysfunction and secondary carnitine
deficiency observed in the subset of autistic patients with an
inverted duplication of chromosome 15q11-q13. In addition, rare
cases of familial autism associated with sudden infant death
syndrome (SIDS) or associated with abnormalities in cellular calcium
homeostasis, such as malignant hyperthermia or cardiac arrhythmia,
are beginning to emerge. Such
special cases suggest that the pathophysiology of autism may
comprise pathways that are directly or indirectly involved in
mitochondrial energy production
and to further probe this connection three new avenues seem worthy
of exploration: 1) metabolomic clinical studies provoking controlled
aerobic exercise stress to expand the biochemical phenotype, 2)
high-throughput expression arrays to directly survey activity of the
genes underlying these biochemical pathways and 3) model systems,
either based upon neuronal stem cells or model genetic organisms, to
discover novel genetic and environmental inputs into these
pathways.

Bridging
from Cells to Cognition in Autism Pathophysiology:
BiologicalPathways
to Defective Brain Function and PlasticityAmerican
Journal of Biochemistry and Biotechnology 4 (2): 167-176,
2008Matthew
P. Anderson, Brian S. Hooker and Martha R. HerbertDepartments
of Neurology and Pathology, Harvard Medical School/Beth Israel
Deaconess Medical Center, Harvard Institutes of Medicine, High
Throughput Biology Team, Fundamental Science Directorate, Pacific
Northwest National Laboratory, Pediatric Neurology/Center for
Morphometric Analysis, Massachusetts General Hospital/Harvard
Medical School, and Center for Child and Adolescent Development,
Cambridge Health Alliance/Harvard Medical SchoolAbstract:
We review evidence to support a model where the disease process
underlying autism may begin when an in utero or early postnatal
environmental, infectious, seizure, or autoimmune insult triggers an
immune response that increases reactive oxygen species (ROS)
production in the brain that leads to DNA damage (nuclear and
mitochondrial) and metabolic enzyme blockade and that these
inflammatory and oxidative stressors persist beyond early
development (with potential further exacerbations), producing
ongoing functional consequences. In organs with a high metabolic
demand such as the central nervous system, the continued use of
mitochondria with damaged DNA and impaired metabolic enzyme function
may generate additional ROS which will cause persistent activation
of the innate immune system leading to more ROS production. Such a
mechanism would self-sustain and possibly progressively worsen. The
mitochondrial dysfunction and altered redox signal transduction
pathways found in autism would conspire to activate both astroglia
and microglia. These activated cells can then initiate a
broad-spectrum proinflammatory gene response. Beyond the direct
effects of ROS on neuronal function, receptors on neurons that bind
the inflammatory mediators may serve to inhibit neuronal signaling
to protect them from excitotoxic damage during various
pathologic insults (e.g., infection).In
autism, over-zealous neuroinflammatory responses could not only
influence neural developmental processes, but may more significantly
impair neural signaling involved in cognition in an ongoing fashion.
This
model makes specific predictions in patients and experimental animal
models and suggests a number of targets sites of intervention. Our
model of potentially reversible pathophysiological mechanisms in
autism motivates our hope that effective therapies may soon appear
on the horizon.

Heavy-Metal
Toxicity—With Emphasis on MercuryJohn
Neustadt, ND, and Steve Pieczenik, MD, PhDResearch
ReviewConclusion:
Metals are ubiquitous in our environment, and exposure to them is
inevitable. However, not all people accumulate toxic levels of
metals or exhibit symptoms of metal toxicity, suggesting that
genetics play a role in their potential to damage health.Metal
toxicity creates multisystem dysfunction, which appears to be
mediated primarily through mitochondrial damage from glutathione
depletion.Accurate
screening can increase the likelihood that patients with potential
metal toxicity are identified. The most accurate screening method
for assessing chronic-metals exposure and metals load in the body is
a provoked urine test.

Evidence
of Mitochondrial Dysfunction in Autism and Implications for
TreatmentAmerican
Journal of Biochemistry and Biotechnology 4 (2): 208-217,
2008Daniel
A. Rossignol, J. Jeffrey Bradstreet, International Child Development
Resource Center,AbstractClassical
mitochondrial diseases occur in a subset of individuals with autism
and are usually caused by genetic anomalies or mitochondrial
respiratory pathway deficits. However, in many cases of autism,
there is evidence of mitochondrial dysfunction (MtD) without the
classic features associated with mitochondrial disease. MtD appears
to be more common in autism and presents with less severe signs and
symptoms. It is not associated with discernable mitochondrial
pathology in muscle biopsy specimens despite objective evidence of
lowered mitochondrial functioning.Exposure
to environmental toxins is the likely etiology for MtD in autism.
This dysfunction then contributes to a number of diagnostic symptoms
and comorbidities observed in autism including: cognitive
impairment, language deficits, abnormal energy metabolism, chronic
gastrointestinal problems, abnormalities in fatty acid oxidation,
and increased oxidative stress. MtD and oxidative stress may also
explain the high male to female ratio found in autism due to
increased male vulnerability to these dysfunctions.Biomarkers
for mitochondrial dysfunction have been identified, but seem widely
under-utilized despite available therapeutic interventions.
Nutritional supplementation to decrease oxidative stress along with
factors to improve reduced glutathione, as well as hyperbaric oxygen
therapy (HBOT) represent supported and rationale approaches. The
underlying pathophysiology and autistic symptoms of affected
individuals would be expected to either improve or cease worsening
once effective treatment for MtD is implemented.

Proximity
to point sources of environmental mercury release as a predictor of
autism prevalenceHealth
& Place, 2008Raymond
F. Palmer, Stephen Blanchard, Robert WoodUniversity
of Texas Health Science Center, San Antonio Department of Family and
Community Medicine, Our Lady of the Lake University, San Antonio
Texas, Chair, Department of SociologyThis
study should be viewed as hypothesis-generating - a first step in
examining the potential role of environmental mercury and childhood
developmental disorders. Nothing is known about specific exposure
routes, dosage, timing, and individual susceptibility.We
suspect that persistent low-dose exposures to various environmental
toxicants, including mercury, that occur during critical windows of
neural development among genetically susceptible children (with a
diminished capacity for metabolizing accumulated toxicants) may
increase the risk for developmental disorders such as
autism.Successfully
identifying the specific combination of environmental exposures and
genetic susceptibilities can inform the development of targeted
prevention intervention strategies.

Epidemiology
of autism spectrum disorder in Portugal: prevalence, clinical
characterization, and medical conditionsDevelopmental
Medicine & Child Neurology, 2007Guiomar
Oliveira MD PhD, Centro de Desenvolvimento da Criança, Hospital
Pediátrico de Coimbra; Assunção Ataíde BSc, Direcção Regional
de Educação do Centro Coimbra;Carla
Marques MSc, Centro de Desenvolvimento da Criança, Hospital
Pediátrico de Coimbra; Teresa S Miguel BSc, Direcção Regional de
Educação do Centro, Coimbra;Ana
Margarida Coutinho BSc, Instituto Gulbenkian de Ciência, Oeiras;
Luísa Mota-Vieira PhD, Unidade de Genética e Patologia
moleculares, Hospital do Divino Espírito Santo, Ponta Delgada,
Açores; Esmeralda Gonçalves PhD; Nazaré Mendes Lopes PhD,
Faculdade de Ciências e Tecnologia, Universidade de Coimbra; Vitor
Rodrigues MD PhD; Henrique Carmona da Mota MD PhD, Faculdade de
Medicina, Universidade de Coimbra, Coimbra; Astrid Moura Vicente
PhD, Instituto Gulbenkian de Ciência, Oeiras,
Portugal.*Correspondence
to first author at Hospital Pediátrico de Coimbra, Av Bissaya
Barreto, 3000-076 Coimbra, Portugal. E-mail:
guiomar@hpc.chc.min-saude.ptAbstract:
The objective of this study was to estimate the prevalence of
autistic spectrum disorder (ASD) and identify its clinical
characterization, and medical conditions in a paediatric population
in Portugal. A school survey was conducted in elementary schools,
targeting 332 808 school-aged children in the mainland and 10 910 in
the Azores islands. Referred children were directly assessed using
the Diagnostic and Statistical Manual of Mental Disorders (4th edn),
the Autism Diagnostic Interview–Revised, and the Childhood Autism
Rating Scale. Clinical history and a laboratory investigation was
performed. In parallel, a systematic multi-source search of children
known to have autism was carried out in a restricted region. The
global prevalence of ASD per 10 000 was 9.2 in mainland, and 15.6 in
the Azores, with intriguing regional differences.A
diversity of associated medical conditions was documented in 20%,
with an unexpectedly high rate of mitochondrial respiratory chain
disorders.

Thimerosal
induces neuronal cell apoptosis by causing cytochrome c and
apoptosis-inducing factor release from mitochondria.International
Journal of Molecular Medicine, 2006Yel
L, Brown LE, Su K, Gollapudi S, Gupta S.Department of Medicine,
University of California, Irvine, CA 92697, USA. lyel@uci.eduThere
is a worldwide increasing concern over the neurological risks of
thimerosal (ethylmercury thiosalicylate) which is an organic mercury
compound that is commonly used as an antimicrobial preservative. In
this study, we show that thimerosal, at nanomolar concentrations,
induces neuronal cell death through the mitochondrial pathway.
Thimerosal, in a concentration- and time-dependent manner, decreased
cell viability as assessed by calcein-ethidium staining and caused
apoptosis detected by Hoechst 33258 dye. Thimerosal-induced
apoptosis was associated with depolarization of mitochondrial
membrane, generation of reactive oxygen species, and release of
cytochrome c and apoptosis-inducing factor (AIF) from mitochondria
to cytosol. Although thimerosal did not affect cellular expression
of Bax at the protein level, we observed translocation of Bax from
cytosol to mitochondria. Finally, caspase-9 and caspase-3 were
activated in the absence of caspase-8 activation. Our data suggest
that thimerosal causes apoptosis in neuroblastoma cells by changing
the mitochondrial microenvironment.

Mitochondrial
mediated thimerosal-induced apoptosis in a human neuroblastoma cell
line (SK-N-SH).Neurotoxicology.
2005Humphrey
ML, Cole MP, Pendergrass JC, Kiningham KK. Department of
Pharmacology, Joan C. Edwards School of Medicine, Marshall
University, Huntington, WV 25704-9388, USA.Environmental
exposure to mercurials continues to be a public health issue due to
their deleterious effects on immune, renal and neurological
function. Recently the safety of thimerosal, an ethyl
mercury-containing preservative used in vaccines, has been
questioned due to exposure of infants during immunization.
Mercurials have been reported to cause apoptosis in cultured
neurons; however, the signaling pathways resulting in cell death
have not been well characterized. Therefore, the objective of this
study was to identify the mode of cell death in an in vitro model of
thimerosal-induced neurotoxicity, and more specifically, to
elucidate signaling pathways which might serve as pharmacological
targets. Within 2 h of thimerosal exposure (5 microM) to the human
neuroblastoma cell line, SK-N-SH, morphological changes, including
membrane alterations and cell shrinkage, were observed. Cell
viability, assessed by measurement of lactate dehydrogenase (LDH)
activity in the medium, as well as the
3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT)
assay, showed a time- and concentration-dependent decrease in cell
survival upon thimerosal exposure. In cells treated for 24 h with
thimerosal, fluorescence microscopy indicated cells undergoing both
apoptosis and oncosis/necrosis. To identify the apoptotic pathway
associated with thimerosal-mediated cell death, we first evaluated
the mitochondrial cascade, as both inorganic and organic mercurials
have been reported to accumulate in the organelle. Cytochrome c was
shown to leak from the mitochondria, followed by caspase 9 cleavage
within 8 h of treatment. In addition, poly(ADP-ribose) polymerase
(PARP) was cleaved to form a 85 kDa fragment following maximal
caspase 3 activation at 24 h. Taken together these findings suggest
deleterious effects on the cytoarchitecture by thimerosal and
initiation of mitochondrial-mediated apoptosis.

Possible
Immunological Disorders in Autism: Concomitant Autoimmunity and
Immune ToleranceThe
Egyptian Journal of Immunology, 2006Maha
I. Sh. Kawashti, Omnia R. Amin Nadia G. RowehyMicrobiology
Department, Faculty of Medicine (For Girls), Al Azhar University,
Cairo, Egypt, Psychiatry Department, Faculty of Medicine, Cairo
University, Cairo, Egypt and Serology Lab King Fahad General
Hospital, Jeddah, K.S.A.Abstract:
Autism is a pervasive developmental disorder that affect children
early in their life. Immunological disorders is one of several
contributing factors that have been suggested to cause autism.
Thirty autistic children aged 3-6 years and thirty non-autistic
psychologically-free siblings were studied. Circulating IgA and IgG
autoantibodies to casein and gluten dietary proteins were detected
by enzyme-immunoassays (EIA). Circulating IgG antibodies to measles,
mumps and rubella vaccine (M.M.R) and cytomeglovirus were
investigated by EIA. Results revealed high seropositivity for
autoantibodies to casein and gluten: 83.3% and 50% respectively in
autistic children as compared to 10% and 6.7% positivity in the
control group. Surprisingly, circulating anti-measles, anti-mumps
and anti-rubella IgG were positive in only 50%, 73.3% and 53.3%
respectively as compared to 100% positivity in the control group.
Anti-CMV IgG was positive in 43.3% of the autistic children as
compared to 7% in the control group. It is concluded that,
autoimmune response to dietary proteins and deficient immune
response to measles, mumps and rubella vaccine antigens might be
associated with autism, as a leading cause or a resulting event.
Further research is needed to confirm these findings.

AbstractBackground:
Macaques are commonly used in pre-clinical vaccine safety testing,
but the combined childhood vaccine regimen, rather than individual
vaccines, has not been studied. Childhood vaccines are a possible
causal factor in autism, and abnormal behaviors and anomalous
amygdala growth are potentially inter-related features of this
condition.Objectives:
The objective of this study was to compare early infant cognition
and behavior with amygdala size and opioid binding in rhesus
macaques receiving the recommended childhood vaccines (1994-1999),
the majority of which contained the bactericidal preservative
ethylmercurithiosalicylic acid (thimerosal).Methods:
Macaques were administered the recommended infant vaccines, adjusted
for age and thimerosal dose (exposed; N=13), or saline (unexposed;
N=3). Primate development, cognition and social behavior were
assessed for both vaccinated and unvaccinated infants using
standardized tests developed at the Washington National Primate
Research Center. Amygdala growth and binding were measured serially
by MRI and by the binding of the non-selective opioid antagonist
[11C]diprenorphine, measured by PET, respectively, before (T1) and
after (T2) the administration of the measles-mumps-rubella vaccine
(MMR).Results:Compared
with unexposed animals, significant neurodevelopmental deficits were
evident for exposed animals in survival reflexes, tests of color
discrimination and reversal, and learning sets. Differences in
behaviors were observed between exposed and unexposed animals and
within the exposed group before and after MMR vaccination. Compared
with unexposed animals, exposed animals showed attenuation of
amygdala growth and differences in the amygdala binding of
[11C]diprenorphine. Interaction models identified significant
associations between specific aberrant social and non-social
behaviors, isotope binding, and vaccine exposure.Conclusions:This
animal model, which examines for the first time, behavioral,
functional, and neuromorphometric consequences of the childhood
vaccine regimen, mimics certain neurological abnormalities of
autism. The findings raise important safety issueswhile
providing a potential model for examining aspects of causation and
disease pathogenesis in acquired disorders of behavior and
development.

AbstractThe
study evaluated possible associations between neurodevelopmental
disorders (NDs) and exposure to mercury (Hg) from
Thimerosal-containing vaccines (TCVs) by examining the automated
Vaccine Safety Datalink (VSD). A total of 278,624 subjects were
identified in birth cohorts from 1990-1996 that had received their
first oral polio vaccination by 3 months of age in the VSD. The
birth cohort prevalence rate of medically diagnosed International
Classification of Disease, 9th revision (ICD-9) specific NDs and
control outcomes were calculated. Exposures to Hg from TCVs were
calculated by birth cohort for specific exposure windows from
birth-7 months and birth-13 months of age. Poisson regression
analysis was used to model the association between the prevalence of
outcomes and Hg doses from TCVs.Consistent
significantly increased rate ratios were observed for autism, autism
spectrum disorders, tics, attention deficit disorder, and emotional
disturbances with Hg exposure from TCVs.By
contrast, none of the control outcomes had significantly increased
rate ratios with Hg exposure from TCVs. Routine childhood
vaccination should be continued to help reduce the morbidity and
mortality associated with infectious diseases, but efforts should be
undertaken to remove Hg from vaccines. Additional studies should be
conducted to further evaluate the relationship between Hg exposure
and NDs.

AbstractThere
is significant evidence that the pathogenesis of several
neurodegenerative diseases, including Parkinson's disease,
Alzheimer's disease, Friedreich's ataxia and amyotrophic lateral
sclerosis, may involve the generation of reactive oxygen species and
mitochondrial dysfunction.Here,
we review the evidence for a disturbance of glutathione homeostasis
that may either lead to or result from oxidative stress in
neurodegenerative disorders. Glutathione is an important
intracellular antioxidant that protects against a variety of
different antioxidant species. An important role for glutathione was
proposed for the pathogenesis of Parkinson's disease, because a
decrease in total glutathione concentrations in the substantia nigra
has been observed in preclinical stages, at a time at which other
biochemical changes are not yet detectable. Because glutathione does
not cross the blood-brain barrier other treatment options to
increase brain concentrations of glutathione including glutathione
analogs, mimetics or precursors are discussed.

AbstractThis study investigated the association
between vaccination with the Hepatitis B triple series vaccine prior
to 2000 and developmental disability in children aged 1–9 years (n
= 1824), proxied by parental report that their child receives early
intervention or special education services (EIS). National Health
and Nutrition Examination Survey 1999–2000 data were analyzed and
adjusted for survey design by Taylor Linearization using SAS version
9.1 software, with SAS callable SUDAAN version 9.0.1. The odds of
receiving EIS were approximately nine times as great for vaccinated
boys (n = 46) as for unvaccinated boys (n = 7), after adjustment for
confounders. This
study found statistically significant evidence to suggest that boys
in United States who were vaccinated with the triple series
Hepatitis B vaccine, during the time period in which vaccines were
manufactured with thimerosal, were more susceptible to developmental
disability than were unvaccinated boys.

Induction
of metallothionein in mouse cerebellum and cerebrum with low-dose
thimerosal injection.Minami
T, Miyata E, Sakamoto Y, Yamazaki H, Ichida S., Department of Life
Sciences, School of Science & Engineering, Kinki University,
3-4-1 Kowakae, Higashi-osaka, Osaka, 577-8502, Japan,
minamita@life.kindai.ac.jp.Cell
Biology and Toxicology. 2009 Apr 9. [Epub ahead of
print]AbstractThimerosal,
an ethyl mercury compound, is used worldwide as a vaccine
preservative. We previously observed that the mercury concentration
in mouse brains did not increase with the clinical dose of
thimerosal injection, but the concentration increased in the brain
after the injection of thimerosal with lipopolysaccharide, even if a
low dose of thimerosal was administered. Thimerosal may penetrate
the brain, but is undetectable when a clinical dose of thimerosal is
injected; therefore, the induction of metallothionein (MT) messenger
RNA (mRNA) and protein was observed in the cerebellum and cerebrum
of mice after thimerosal injection, as MT is an inducible protein.
MT-1 mRNA was expressed at 6 and 9 h in both the cerebrum and
cerebellum, but MT-1 mRNA expression in the cerebellum was three
times higher than that in the cerebrum after the injection of 12
microg/kg thimerosal. MT-2 mRNA was not expressed until 24 h in both
organs. MT-3 mRNA was expressed in the cerebellum from 6 to 15 h
after the injection, but not in the cerebrum until 24 h. MT-1 and
MT-3 mRNAs were expressed in the cerebellum in a dose-dependent
manner. Furthermore, MT-1 protein was detected from 6 to 72 h in the
cerebellum after 12 microg/kg of thimerosal was injected and peaked
at 10 h. MT-2 was detected in the cerebellum only at 10 h. In the
cerebrum, little MT-1 protein was detected at 10 and 24 h, and there
were no peaks of MT-2 protein in the cerebrum. In conclusion, MT-1
and MT-3 mRNAs but not MT-2 mRNA are easily expressed in the
cerebellum rather than in the cerebrum by the injection of low-dose
thimerosal. It is thought that the cerebellum is a sensitive organ
against thimerosal.As
a result of the present findings, in combination with the brain
pathology observed in patients diagnosed with autism, the present
study helps to support the possible biological plausibility for how
low-dose exposure to mercury from thimerosal-containing vaccines may
be associated with autism.

AbstractThis
longitudinal, case-control pilot study examined amygdala growth in
rhesus macaque infants receiving the complete US childhood vaccine
schedule (1994-1999). Longitudinal structural and functional
neuroimaging was undertaken to examine central effects of the
vaccine regimen on the developing brain. Vaccine-exposed and
saline-injected control infants underwent MRI and PET imaging at
approximately 4 and 6 months of age, representing two specific
timeframes within the vaccination schedule. Volumetric analyses
showed that exposed animals did not undergo the maturational changes
over time in amygdala volume that was observed in unexposed animals.
After controlling for left amygdala volume, the binding of the
opioid antagonist [11C]diprenorphine (DPN) in exposed animals
remained relatively constant over time, compared with unexposed
animals, in which a significant decrease in [11C]DPN binding
occurred.These
results suggest that maturational changes in amygdala volume and the
binding capacity of [11C]DPN in the amygdala was significantly
altered in infant macaques receiving the vaccine schedule. The
macaque infant is a relevant animal model in which to investigate
specific environmental exposures and structural/functional
neuroimaging during neurodevelopment.

AbstractThere
are reports suggesting that some autistic children are unable to
mount an adequate response following exposure to environmental
toxins. This potential deficit, coupled with the similarity in
clinical presentations of autism and some heavy metal toxicities,
has led to the suggestion that heavy metal poisoning might play a
role in the etiology of autism in uniquely susceptible individuals.
Thimerosal, an anti-microbial preservative previously added
routinely to childhood multi-dose vaccines, is composed of 49.6%
ethyl mercury. Based on the levels of this toxin that children
receive through routine immunization schedules in the first years of
life, it has been postulated that thimerosal may be a potential
triggering mechanism contributing to autism in susceptible
individuals. One potential risk factor in these individuals may be
an inability to adequately up-regulate metallothionein (MT)
biosynthesis in response to presentation of a heavy metal challenge.
To investigate this hypothesis, cultured lymphocytes (obtained from
the Autism Genetic Resource Exchange, AGRE) from autistic children
and non-autistic siblings were challenged with either 10 microM
ethyl mercury, 150 microM zinc, or fresh media (control). Following
the challenge, total RNA was extracted and used to query "whole
genome" DNA microarrays. Cultured lymphocytes challenged with
zinc responded with an impressive up-regulation of MT transcripts
(at least nine different MTs were over-expressed)while
cells challenged with thimerosal responded by up-regulating numerous
heat shock protein transcripts, but not MTs. Although there were no
apparent differences between autistic and non-autistic sibling
responses in this very small sampling group, the differences in
expression profiles between those cells treated with zinc versus
thimerosal were dramatic.Determining
cellular response, at the level of gene expression, has important
implications for the understanding and treatment of conditions that
result from exposure to neurotoxic compounds.

Sorting
out the spinning of autism: heavy metals and the question of
incidenceActa
Neurobiol Exp 2010, 70: 165–176Mary
Catherine DeSoto* and Robert T. Hitlan, Department of Psychology,
University of Northern Iowa, Cedar Falls, Iowa, USAThe
reasons for the rise in autism prevalence are a subject of heated
professional debate. Featuring a critical appraisal of some research
used to question whether there is a rise in cases and if rising
levels of autism are related to environmentalexposure
to toxins (Soden et al. 2007, Thompson et al. 2007, Barbaresi et al.
2009) we aim to evaluate the actual state of scientific knowledge.
In addition, we surveyed the empirical research on the topic of
autism and heavy metal toxins. Overall, the various causes that have
led to the increase in autism diagnosis are likely multi-faceted,
and understanding the causes is one of the most important health
topics today. We argue that scientific research does not support
rejecting the link between the neurodevelopmental disorder of autism
and toxic exposures.

Urinary
Porphyrin Excretion in Neurotypical and Autistic ChildrenEnviron
Health Perspect. 2010 Oct;118(10):1450-7. Epub 2010 Jun 24.Woods
JS, Armel SE, Fulton DI, Allen J, Wessels K, Simmonds PL,
Granpeesheh D, Mumper E, Bradstreet JJ, Echeverria D, Heyer NJ,
Rooney JP., Department of Environmental and Occupational Health
Sciences, University of WashingtonAbstractBACKGROUND:
Increased urinary concentrations of pentacarboxyl-, precopro- and
copro-porphyrins have been associated with prolonged mercury (Hg)
exposure in adults, and comparable increases have been attributed to
Hg exposure in children with autism (AU).OBJECTIVES:
This study was designed to measure and compare urinary porphyrin
concentrations in neurotypical (NT) children and same-age children
with autism, and to examine the association between porphyrin levels
and past or current Hg exposure in children with autism.METHODS:
This exploratory study enrolled 278 children 2-12 years of age. We
evaluated three groups: AU, pervasive developmental disorder-not
otherwise specified (PDD-NOS), and NT. Mothers/caregivers provided
information at enrollment regarding medical, dental, and dietary
exposures. Urine samples from all children were acquired for
analyses of porphyrin, creatinine, and Hg. Differences between
groups for mean porphyrin and Hg levels were evaluated. Logistic
regression analysis was conducted to determine whether porphyrin
levels were associated with increased risk of autism.RESULTS:
Mean urinary porphyrin concentrations are naturally high in young
children and decline by as much as 2.5-fold between 2 and 12 years
of age. Elevated copro- (p < 0.009), hexacarboxyl- (p < 0.01)
and pentacarboxyl- (p < 0.001) porphyrin concentrations were
significantly associated with AU but not with PDD-NOS. No
differences were found between NT and AU in urinary Hg levels or in
past Hg exposure as determined by fish consumption, number of dental
amalgam fillings, or vaccines received. CONCLUSIONS:These
findings identify disordered porphyrin metabolism as a salient
characteristic of autism.Hg
exposures were comparable between diagnostic groups, and a porphyrin
pattern consistent with that seen in Hg-exposed adults was not
apparent.

Mitochondrial
dysfunction in autism spectrum disorders: a systematic review and
meta-analysisMolecular
Psychiatry advance online publication 25 January 2011;doi:
10.1038/mp.2010.136D
A Rossignol and R E FryeAbstractA
comprehensive literature search was performed to collate evidence of
mitochondrial dysfunction in autism spectrum disorders (ASDs) with
two primary objectives. First, features of mitochondrial dysfunction
in the general population of children with ASD were identified.
Second, characteristics of mitochondrial dysfunction in children
with ASD and concomitant mitochondrial disease (MD) were compared
with published literature of two general populations: ASD children
without MD, and non-ASD children with MD. The prevalence of MD in
the general population of ASD was 5.0% (95% confidence interval 3.2,
6.9%), much higher than found in the general population (~0.01%).
The prevalence of abnormal biomarker values of mitochondrial
dysfunction was high in ASD, much higher than the prevalence of MD.
Variances and mean values of many mitochondrial biomarkers (lactate,
pyruvate, carnitine and ubiquinone) were significantly different
between ASD and controls. Some markers correlated with ASD severity.
Neuroimaging, in vitro and post-mortem brain studies were consistent
with an elevated prevalence of mitochondrial dysfunction in ASD.
Taken together, these findings suggest children with ASD have a
spectrum of mitochondrial dysfunction of differing severity.
Eighteen publications representing a total of 112 children with ASD
and MD (ASD/MD) were identified. The prevalence of developmental
regression (52%), seizures (41%), motor delay (51%),
gastrointestinal abnormalities (74%), female gender (39%), and
elevated lactate (78%) and pyruvate (45%) was significantly higher
in ASD/MD compared with the general ASD population. The prevalence
of many of these abnormalities was similar to the general population
of children with MD, suggesting that ASD/MD represents a distinct
subgroup of children with MD. Most ASD/MD cases (79%) were not
associated with genetic abnormalities, raising the possibility of
secondary mitochondrial dysfunction. Treatment studies for ASD/MD
were limited, although improvements were noted in some studies with
carnitine, co-enzyme Q10 and B-vitamins. Many studies suffered from
limitations, including small sample sizes, referral or publication
biases, and variability in protocols for selecting children for MD
workup, collecting mitochondrial biomarkers and defining
MD.Overall,
this evidence supports the notion that mitochondrial dysfunction is
associated with ASD.Additional
studies are needed to further define the role of mitochondrial
dysfunction in ASD.

Sensitization
effect of thimerosal is mediated in vitro via reactive oxygen
species and calcium signaling.Toxicology.
2010 July - August;274(1-3):1-9. Epub 2010 May 10.Migdal
C, Foggia L, Tailhardat M, Courtellemont P, Haftek M, Serres
M.Thimerosal,
a mercury derivative composed of ethyl mercury chloride (EtHgCl) and
thiosalicylic acid (TSA), is widely used as a preservative in
vaccines and cosmetic products and causes cutaneous reactions. Since
dendritic cells (DCs) play an essential role in the immune response,
the sensitization potency of chemicals was studied in vitro using
U937, a human promyelomonocytic cell line that is used as a
surrogate of monocytic differentiation and activation. Currently,
this cell line is under ECVAM (European Center for the Validation of
Alternative Methods) validation as an alternative method for
discriminating chemicals. Thimerosal and mercury derivatives induced
in U937 an overexpression of CD86 and interleukin (IL)-8 secretion
similarly to 1-chloro-2,4-dinitrobenzene (DNCB), a sensitizer used
as a positive control for DC activation. Non-sensitizers,
dichloronitrobenzene (DCNB), TSA and sodium dodecyl sulfate (SDS),
an irritant, had no effect. U937 activation was prevented by cell
pretreatment with N-acetyl-l-cysteine (NAC) but not with
thiol-independent antioxidants except vitamin E which affected CD86
expression by preventing lipid peroxidation of cell membranes.
Thimerosal, EtHgCl and DNCB induced glutathione (GSH) depletion and
reactive oxygen species (ROS) within 15min; another peak was
detected after 2h for mercury compounds only. MitoSOX, a specific
mitochondrial fluorescent probe, confirmed that ROS were essentially
produced by mitochondria in correlation with its membrane
depolarization. Changes in mitochondrial membrane permeability
induced by mercury were reversed by NAC but not by thiol-independent
antioxidants. Thimerosal and EtHgCl also induced a calcium (Ca(2+))
influx with a peak at 3h, suggesting that Ca(2+) influx is a
secondary event following ROS induction as Ca(2+) influx was
suppressed after pretreatment with NAC but not with
thiol-independent antioxidants. Ca(2+) influx was also suppressed
when culture medium was deprived of Ca(2+) confirming the
specificity of the measure.In
conclusion, these data suggest that thimerosal induced U937
activation via oxidative stress from mitochondrial stores and
mitochondrial membrane depolarization with a primordial effect of
thiol groups.A
cross-talk between ROS and Ca(2+) influx was demonstrated.

What's
going on? The question of time trends in autism.

Public
Health Rep. 2004 Nov-Dec;119(6):536-51.

Blaxill
MF.

AbstractIncreases in the reported prevalence of
autism and autistic spectrum disorders in recent years have fueled
concern over possible environmental causes. The author reviews the
available survey literature and finds evidence of large increases in
prevalence in both the United States and the United Kingdom that
cannot be explained by changes in diagnostic criteria or
improvements in case ascertainment. Incomplete ascertainment of
autism cases in young child populations is the largest source of
predictable bias in prevalence surveys; however, this bias has, if
anything, worked against the detection of an upward trend in recent
surveys. Comparison of autism rates by year of birth for specific
geographies provides the strongest basis for trend assessment. Such
comparisons show large recent increases in rates of autism and
autistic spectrum disorders in both the U.S. and the U.K. Reported
rates of autism in the United States increased from < 3 per
10,000 children in the 1970s to > 30 per 10,000 children in the
1990s, a 10-fold increase. In the United Kingdom, autism rates rose
from < 10 per 10,000 in the 1980s to roughly 30 per 10,000 in the
1990s. Reported rates for the full spectrum of autistic disorders
rose from the 5 to 10 per 10,000 range to the 50 to 80 per 10,000
range in the two countries. A precautionary approach suggests that
the rising incidence of autism should be a matter of urgent public
concern.

Excerpt: "Vaccinations
may be one of the triggers for autism. Substantial data demonstrate
immune abnormality in many autistic children consistent with
impaired resistance to infection, activation of inflammatory
response, and autoimmunity. Impaired resistance may predispose to
vaccine injury in autism."

Theoretical
aspects of autism: Causes—A reviewJournal
of Immunotoxicology, January-March 2011, Vol. 8, No. 1 , Pages
68-79Helen
V. Ratajczak, PhDAutism,
a member of the pervasive developmental disorders (PDDs), has been
increasing dramatically since its description by Leo Kanner in 1943.
First estimated to occur in 4 to 5 per 10,000 children, the
incidence of autism is now 1 per 110 in the United States, and 1 per
64 in the United Kingdom, with similar incidences throughout the
world. Searching information from 1943 to the present in PubMed and
Ovid Medline databases, this review summarizes results that
correlate the timing of changes in incidence with environmental
changes. Autism could result from more than one cause, with
different manifestations in different individuals that share common
symptoms. Documented causes of autism include genetic mutations
and/or deletions, viral infections, and encephalitis following
vaccination.Therefore,
autism is the result of genetic defects and/or inflammation of the
brain. The inflammation could be caused by a defective placenta,
immature blood-brain barrier, the immune response of the mother to
infection while pregnant, a premature birth, encephalitis in the
child after birth, or a toxic environment.

Ancestry
of pink disease (infantile acrodynia) identified as a risk factor
for autism spectrum disorders.J
Toxicol Environ Health A. 2011 Sep 15;74(18):1185-94.Shandley
K, Austin DW.Swinburne
Autism Bio-Research Initiative (SABRI), Brain and Psychological
Sciences Research Centre , Swinburne University of Technology ,
Hawthorn , Victoria , Australia.AbstractPink
disease (infantile acrodynia) was especially prevalent in the first
half of the 20th century. Primarily attributed to exposure to
mercury (Hg) commonly found in teething powders, the condition was
developed by approximately 1 in 500 exposed children. The
differential risk factor was identified as an idiosyncratic
sensitivity to Hg. Autismspectrum disorders (ASD) have also been
postulated to be produced by Hg. Analogous to the pink disease
experience, Hg exposure is widespread yet only a fraction of exposed
children develop an ASD, suggesting sensitivity to Hg may also be
present in children with an ASD. The objective of this study was to
test the hypothesis that individuals with a known hypersensitivity
to Hg (pink disease survivors) may be more likely to have
descendants with an ASD. Five hundred and twenty-two participants
who had previously been diagnosed with pink disease completed a
survey on the health outcomes of their descendants. The prevalence
rates of ASD and a variety of other clinical conditions diagnosed in
childhood (attention deficit hyperactivity disorder, epilepsy,
Fragile X syndrome, and Down syndrome) were compared to
well-established general population prevalence rates. The results
showed the prevalence rate of ASD among the grandchildren of pink
disease survivors (1 in 22) to be significantly higher than the
comparable general population prevalence rate (1 in 160).The
results support the hypothesis that Hg sensitivity may be a
heritable/genetic risk factor for ASD.

The
rate of febrile seizures increases following measles, mumps, and
rubella (MMR) vaccination
but it is unknown whether the rate varies according to personal or
family history of seizures, perinatal factors, or socioeconomic
status. Furthermore, little is known about the long-term outcome of
febrile seizures following vaccination.

OBJECTIVES:

To
estimate incidence rate ratios (RRs) and risk differences of febrile
seizures following MMR vaccination within subgroups of children and
to evaluate the clinical outcome of febrile seizures following
vaccination.

DESIGN,
SETTING, AND PARTICIPANTS:

A
population-based cohort study of all children born in Denmark between
January 1, 1991, and December 31, 1998, who were alive at 3 months;
537,171 children were followed up until December 31, 1999, by using
data from the Danish Civil Registration System and 4 other national
registries.

A
total of 439,251 children (82%) received MMR vaccination and 17,986
children developed febrile seizures at least once; 973 of these
febrile seizures occurred within 2 weeks of MMR vaccination. The RR
of febrile seizures increased during the 2 weeks following MMR
vaccination (2.75; 95% confidence interval [CI], 2.55-2.97), and
thereafter was close to the observed RR for nonvaccinated children.
The RR did not vary significantly in the subgroups of children that
had been defined by their family history of seizures, perinatal
factors, or socioeconomic status. At 15 to 17 months, the risk
difference of febrile seizures within 2 weeks following MMR
vaccination was 1.56 per 1000 children overall (95% CI, 1.44-1.68),
3.97 per 1000 (95% CI, 2.90-5.40) for siblings of children with a
history of febrile seizures, and 19.47 per 1000 (95% CI, 16.05-23.55)
for children with a personal history of febrile seizures. Children
with febrile seizures following MMR vaccinations had a slightly
increased rate of recurrent febrile seizures (RR, 1.19; 95% CI,
1.01-1.41) but no increased rate of epilepsy (RR, 0.70; 95% CI,
0.33-1.50) compared with children who were nonvaccinated at the time
of their first febrile seizure.

CONCLUSIONS:

MMR
vaccination was associated with a transient increased rate of febrile
seizures
but the risk difference was small even in high-risk children. The
long-term rate of epilepsy was not increased in children who had
febrile seizures following vaccination compared with children who had
febrile seizures of a different etiology.

Adverse
events following 12 and 18 month vaccinations: a population-based,
self-controlled case series analysis.PLoS
One. 2011;6(12):e27897. Epub 2011 Dec 12.Wilson
K, Hawken S, Kwong JC, Deeks S, Crowcroft NS, Van Walraven C, Potter
BK, Chakraborty P, Keelan J, Pluscauskas M, Manuel D. Department of
Medicine, Ottawa Hospital Research Institute, University of Ottawa,
Ottawa, Canada. kwilson@ohri.caAbstractBACKGROUND:Live
vaccines have distinct safety profiles, potentially causing systemic
reactions one to 2 weeks after administration. In the province of
Ontario, Canada, live MMR vaccine is currently recommended at age 12
months and 18 months.METHODS:Using
the self-controlled case series design we examined 271,495 12 month
vaccinations and 184,312 18 month vaccinations to examine the
relative incidence of the composite endpoint of emergency room
visits or hospital admissions in consecutive one day intervals
following vaccination. These were compared to a control period 20 to
28 days later. In a post-hoc analysis we examined the reasons for
emergency room visits and the average acuity score at presentation
for children during the at-risk period following the 12 month
vaccine.RESULTS:Four
to 12 days post 12 month vaccination, children had a 1.33
(1.29-1.38) increased relative incidence of the combined endpoint
compared to the control period, or at least one event during the
risk interval for every 168 children vaccinated. Ten to 12 days post
18 month vaccination, the relative incidence was 1.25 (95%,
1.17-1.33) which represented at least one excess event for every 730
children vaccinated. The primary reason for increased events was
statistically significant elevations in emergency room visits
following all vaccinations. There were non-significant increases in
hospital admissions.There
were an additional 20 febrile seizures for every 100,000 vaccinated
at 12 months.CONCLUSIONS:There
are significantly elevated risks of primarily emergency room visits
approximately one to two weeks following 12 and 18 month
vaccination. Future studies should examine whether these events
could be predicted or prevented.

Administration
of thimerosal to infant rats increases overflow of glutamate and
aspartate in the prefrontal cortex: protective role of
dehydroepiandrosterone sulfate.Neurochem
Res. 2012 Feb;37(2):436-47. Epub 2011 Oct 21.Duszczyk-Budhathoki
M, Olczak M, Lehner M, Majewska MD. Marie Curie Chairs
Program, Department of Pharmacology and Physiology of Nervous
System, Institute of Psychiatry and Neurology, 02-957, Warsaw,
Poland.AbstractThimerosal,
a mercury-containing vaccine preservative, is a suspected factor in
the etiology of neurodevelopmental disorders. We previously showed
that its administration to infant rats causes behavioral,
neurochemical and neuropathological abnormalities similar to those
present in autism. Here we examined, using microdialysis, the effect
of thimerosal on extracellular levels of neuroactive amino acids in
the rat prefrontal cortex (PFC). Thimerosal administration (4
injections, i.m., 240 μg Hg/kg on postnatal days 7, 9, 11, 15)
induced lasting changes in amino acid overflow: an increase of
glutamate and aspartate accompanied by a decrease of glycine and
alanine; measured 10-14 weeks after the injections. Four injections
of thimerosal at a dose of 12.5 μg Hg/kg did not alter glutamate
and aspartate concentrations at microdialysis time (but based on
thimerosal pharmacokinetics, could have been effective soon after
its injection). Application of thimerosal to the PFC in perfusion
fluid evoked a rapid increase of glutamate overflow.
Coadministration of the neurosteroid, dehydroepiandrosterone sulfate
(DHEAS; 80 mg/kg; i.p.) prevented the thimerosal effect on glutamate
and aspartate; the steroid alone had no influence on these amino
acids. Coapplication of DHEAS with thimerosal in perfusion fluid
also blocked the acute action of thimerosal on glutamate. In
contrast, DHEAS alone reduced overflow of glycine and alanine,
somewhat potentiating the thimerosal effect on these amino
acids.Since
excessive accumulation of extracellular glutamate is linked with
excitotoxicity, our data imply that neonatal exposure to
thimerosal-containing vaccines might induce excitotoxic brain
injuries, leading to neurodevelopmental disorders.DHEAS
may partially protect against mercurials-induced neurotoxicity.

Neonatal
Administration of Thimerosal Causes Persistent Changes in Mu Opioid
Receptors in the Rat BrainNeurochem
Res. 2010 November; 35(11): 1840–1847.Mieszko
Olczak, Michalina Duszczyk, Pawel Mierzejewski, Teresa Bobrowicz,
and Maria Dorota Majewska1, Department of Pharmacology and
Physiology of the Nervous System, Institute of Psychiatry and
Neurology, Sobieskiego 9 str., 02-957 Warsaw, Poland, Department of
Forensic Medicine, Medical University of Warsaw, Oczki 1 str.,
02-007 Warsaw, Poland, Department of Neuropathology, Institute of
Psychiatry and Neurology, 02-957 Warsaw, Poland, Department of
Biology and Environmental Science, University of Cardinal Stefan
Wyszynski, Wóycickiego Str. 1/3, 01-815 Warsaw,
PolandAbstractThimerosal
added to some pediatric vaccines is suspected in pathogenesis of
several neurodevelopmental disorders. Our previous study showed that
thimerosal administered to suckling rats causes persistent,
endogenous opioid-mediated hypoalgesia. Here we examined, using
immunohistochemical staining technique, the density of μ-opioid
receptors (MORs) in the brains of rats, which in the second
postnatal week received four i.m. injections of thimerosal at doses
12, 240, 1,440 or 3,000 μg Hg/kg. The periaqueductal gray, caudate
putamen and hippocampus were examined. Thimerosal administration
caused dose-dependent statistically significant increase in MOR
densities in the periaqueductal gray and caudate putamen, but
decrease in the dentate gyrus, where it was accompanied by the
presence of degenerating neurons and loss of synaptic vesicle marker
(synaptophysin).These
data document that exposure to thimerosal during early postnatal
life produces lasting alterations in the densities of brain opioid
receptors along with other neuropathological changes, which may
disturb brain development.

Unanswered
Questions: A Review of Compensated Cases of Vaccine-Induced Brain
InjuryPace
Environmental Law Review, vol. 28, no. 2, 2011Mary
Holland, Louis Conte, Robert Krakow and Lisa ColinExecutive
SummaryIn
1986, Congress created the Vaccine Injury Compensation Program
(VICP) under the National Childhood Vaccine Injury Act (1986 Law).
This Program has original jurisdiction for children’s claims of
vaccine injury. Because almost all children receive multiple
vaccinations for daycare and school, it is critically important that
the Program provides fundamental fairness, due process and
transparency.This
empirical investigation, published in a peer-reviewed law journal,
examines claims that the VICP compensated for vaccine-induced
encephalopathy and seizure disorder. The VICP has compensated
approximately 2,500 claims of vaccine injury since the inception of
the program. This study found 83 cases of acknowledged
vaccine-induced brain damage that include autism, a disorder that
affects speech, social communication and behavior.In
21 published cases of the Court of Federal Claims, which administers
the VICP, the Court stated that the petitioners had autism or
described autism unambiguously. In 62 remaining cases, the authors
identified settlement agreements where Health and Human Services
(HHS) compensated children with vaccine-induced brain damage, who
also have autism or an autism spectrum disorder.Parents
reported the existence of autism in telephone interviews and
supplied supplemental materials including medical diagnoses, school
records, and completed, standard autism screening questionnaires to
verify their reports. In 39 of the 83 cases, or 47% of the cases of
vaccine injury reviewed, there is confirmation of autism or autism
spectrum disorder beyond parental report.This
finding of autism in compensated cases of vaccine injury is
significant. U.S. government spokespeople have been asserting no
vaccine-autism link for more than a decade. This finding calls into
question the decisions of the Court of Federal Claims in the Omnibus
Autism Proceeding in 2009 and 2010 and the statement of Health and
Human Services on its website that “HHS has never concluded in any
case that autism was caused by vaccination.”Using
publicly available information, the investigation shows that the
VICP has been compensating cases of vaccine-induced brain damage
associated with autism for more than twenty years. This
investigation suggests that officials at HHS, the Department of
Justice and the Court of Federal Claims may have been aware of this
association but failed to publicly disclose it.The
study calls on Congress to thoroughly investigate the VICP,
including a medical investigation of compensated claims of vaccine
injury. This investigation calls on Congress to get answers to these
critically important unanswered questions.

Integrating
experimental (in vitro and in vivo) neurotoxicity studies of
low-dose thimerosal relevant to vaccines.Neurochem
Res.2011
Jun;36(6):927-38. doi: 10.1007/s11064-011-0427-0. Epub 2011 Feb
25.Dórea
JG,
Faculty of Health Sciences, Universidade de Brasília, CP 04322,
70919-970, Brasília, DF, Brazil. dorea@rudah.com.brAbstractThere
is a need to interpret neurotoxic studies to help deal with
uncertainties surrounding pregnant mothers, newborns and young
children who must receive repeated doses of Thimerosal-containing
vaccines (TCVs). This review integrates information derived from
emerging experimental studies (in vitro and in vivo) of low-dose
Thimerosal (sodium ethyl mercury thiosalicylate). Major databases
(PubMed and Web-of-science) were searched for in vitro and in vivo
experimental studies that addressed the effects of low-dose
Thimerosal (or ethylmercury) on neural tissues and animal behaviour.
Information extracted from studies indicates that: (a) activity of
low doses of Thimerosal against isolated human and animal brain
cells was found in all studies and is consistent with Hg
neurotoxicity; (b) the neurotoxic effect of ethylmercury has not
been studied with co-occurring adjuvant-Al in TCVs; (c) animal
studies have shown that exposure to Thimerosal-Hg can lead to
accumulation of inorganic Hg in brain, and that (d) doses relevant
to TCV exposure possess the potential to affect human
neuro-development. Thimerosal at concentrations relevant for
infants' exposure (in vaccines) is toxic to cultured human-brain
cells and to laboratory animals. The persisting use of TCV (in
developing countries) is counterintuitive to global efforts to lower
Hg exposure and to ban Hg in medical products; its continued use in
TCV requires evaluation of a sufficiently nontoxic level of
ethylmercury compatible with repeated exposure (co-occurring with
adjuvant-Al) during early life.

Hepatitis
B vaccine induces apoptotic death in Hepa1-6 cellsApoptosis.
2012 Jan 17. Hamza H, Cao J, Li X, Li C, Zhu M, Zhao S.Key
Lab of Agricultural Animal Genetics, Breeding, and Reproduction of
Ministry of Education, College of Animal Science and Technology,
Huazhong Agricultural University, Wuhan, 430070, People's Republic
of China, Heyam68_hamza@yahoo.com.AbstractVaccines
can have adverse side-effects, and these are predominantly
associated with the inclusion of chemical additives such as aluminum
hydroxide adjuvant. The objective of this study was to establish an
in vitro model system amenable to mechanistic investigations of
cytotoxicity induced by hepatitis B vaccine, and to investigate the
mechanisms of vaccine-induced cell death. The mouse liver hepatoma
cell line Hepa1-6 was treated with two doses of adjuvanted
(aluminium hydroxide) hepatitis B vaccine (0.5 and 1 μg protein per
ml) and cell integrity was measured after 24, 48 and 72 h. Hepatitis
B vaccine exposure increased cell apoptosis as detected by flow
cytometry and TUNEL assay. Vaccine exposure was accompanied by
significant increases in the levels of activated caspase 3, a key
effector caspase in the apoptosis cascade. Early transcriptional
events were detected by qRT-PCR. We report that hepatitis B vaccine
exposure resulted in significant upregulation of the key genes
encoding caspase 7, caspase 9, Inhibitor caspase-activated DNase
(ICAD), Rho-associated coiled-coil containing protein kinase 1
(ROCK-1), and Apoptotic protease activating factor 1 (Apaf-1).
Upregulation of cleaved caspase 3,7 were detected by western blot in
addition to Apaf-1 and caspase 9 expressions argues that cell death
takes place via the intrinsic apoptotic pathway in which release of
cytochrome c from the mitochondria triggers the assembly of a
caspase activation complex.We
conclude that exposure of Hepa1-6 cells to a low dose of adjuvanted
hepatitis B vaccine leads to loss of mitochondrial integrity,
apoptosis induction, and cell death, apoptosis effect was observed
also in C2C12 mouse myoblast cell line after treated with low dose
of vaccine (0.3, 0.1, 0.05 μg/ml).
In addition In vivo apoptotic effect of hepatitis B vaccine was
observed in mouse liver.

EXCERPT: In
recent years, controversy has surrounded the use of thimerosal in
vaccines as mercury is a known neurotoxin and nephrotoxin. Since the
controversy began in the late 1990's, much of the thimerosal has
been removed from vaccines administered to children in the United
States. However, it remains in some, such as the influenza vaccine,
and is added to multidose vials used in countries around the world.
Studies concentrating on thimerosal-induced neurotoxicity are
limited, and exposure guidelines, such as those set by the Food and
Drug Administration, are based on research with methylmercury.
Interestingly, some in vitro and in vivo studies suggest that
ethylmercury may react differently than methylmercury (Aschner and
Aschner, 1990; Harry et al., 2004; Magos et al., 1985). Few studies
with thimerosal have focused on determining specific signaling
pathways involved in neurotoxicity. Establishing these pathways may
be an important step in discovering methods of alleviating toxic
outcomes in patients exposed to thimerosal….Our study is the first
demonstration that thimerosal can induce the activation of JNK and
AP-1 in the SK-N-SH neuroblastoma cell line. We showed that
activation of cJun and AP-1 transcriptional activity following
thimerosal treatment does not appear to be involved in the induction
of apoptosis, as demonstrated with the studies using the cJun
dominant negative. Furthermore, we were able to show that JNK is an
essential upstream component of this pathway through the use of the
JNK inhibitor SP600125. This compound was able to attenuate
activation of downstream components of mitochondrial-mediated cell
death and subsequently protect the cells from apoptosis. These
results are significant because identifying specific signaling
pathways activated in response to thimerosal exposure presents
pharmacological targets for attenuating potential toxicity in
patients exposed to thimerosal-containing products.

Maternal
thimerosal exposure results in aberrant cerebellar oxidative stress,
thyroid hormone metabolism, and motor behavior in rat pups; sex- and
strain-dependent effects.Cerebellum.2012
Jun;11(2):575-86. doi: 10.1007/s12311-011-0319-5.Sulkowski
ZL,Chen
T,Midha
S,Zavacki
AM,Sajdel-Sulkowska
EM,
Department of Psychiatry, Harvard Medical School and Brigham and
Women's Hospital, Boston, MA, USA.AbstractMethylmercury
(Met-Hg) and ethylmercury (Et-Hg) are powerful toxicants with a
range of harmful neurological effects in humans and animals. While
Met-Hg is a recognized trigger of oxidative stress and an endocrine
disruptor impacting neurodevelopment, the developmental
neurotoxicity of Et-Hg, a metabolite of thimerosal (TM), has not
been explored. We hypothesized that TM exposure during the perinatal
period impairs central nervous system development, and specifically
the cerebellum, by the mechanism involving oxidative stress. To test
this, spontaneously hypertensive rats (SHR) or Sprague-Dawley (SD)
rat dams were exposed to TM (200 μg/kg body weight) during
pregnancy (G10-G15) and lactation (P5-P10). Male and female neonates
were evaluated for auditory and motor function; cerebella were
analyzed for oxidative stress and thyroid metabolism. TM exposure
resulted in a delayed startle response in SD neonates and decreased
motor learning in SHR male (22.6%), in SD male (29.8%), and in SD
female (55.0%) neonates. TM exposure also resulted in a significant
increase in cerebellar levels of the oxidative stress marker
3-nitrotyrosine in SHR female (35.1%) and SD male (14.0%) neonates.
The activity of cerebellar type 2 deiodinase, responsible for local
intra-brain conversion of thyroxine to the active hormone,
3',3,5-triiodothyronine (T3), was significantly decreased in
TM-exposed SHR male (60.9%) pups. This coincided with an increased
(47.0%) expression of a gene negatively regulated by T3, Odf4
suggesting local intracerebellar T3 deficiency. Our
data thus demonstrate a negative neurodevelopmental impact of
perinatal TM exposure which appears to be both strain- and
sex-dependent.

Hertz-Picciotto
I,Delwiche
L., Department of Public Health Sciences, University of California,
Davis, California 95616, USA.
ihp@ucdavis.eduAbstractBACKGROUND:Autism
prevalence in California, based on individuals eligible for
state-funded services, rose throughout the 1990s. The extent to
which this trend is explained by changes in age at diagnosis or
inclusion of milder cases has not been previously
evaluated.METHODS:Autism
cases were identified from 1990 through 2006 in databases of the
California Department of Developmental Services, which coordinates
services for individuals with specific developmental disorders. The
main outcomes were population incident cases younger than age 10
years for each quarter, cumulative incidence by age and birth year,
age-specific incidence rates stratified by birth year, and
proportions of diagnoses by age across birth years.RESULTS:Autism
incidence in children rose throughout the period. Cumulative
incidence to 5 years of age per 10,000 births rose consistently from
6.2 for 1990 births to 42.5 for 2001 births. Age-specific incidence
rates increased most steeply for 2- and 3-year olds. The proportion
diagnosed by age 5 years increased only slightly, from 54% for 1990
births to 61% for 1996 births. Changing age at diagnosis can explain
a 12% increase, and inclusion of milder cases, a 56%
increase.CONCLUSIONS:Autism
incidence in California shows no sign yet of plateauing. Younger
ages at diagnosis, differential migration, changes in diagnostic
criteria, and inclusion of milder cases do not fully explain the
observed increases. Other artifacts have yet to be quantified, and
as a result, the extent to which the continued rise represents a
true increase in the occurrence of autism remains unclear.

BackgroundLong-term biodistribution
of nanomaterials used in medicine is largely unknown. This is the
case for alum, the most widely used vaccine adjuvant, which is a
nanocrystalline compound spontaneously forming
micron/submicron-sized agglomerates. Although generally well
tolerated, alum is occasionally detected within monocyte-lineage
cells long after immunization in presumably susceptible individuals
with systemic/neurologic manifestations or autoimmune (inflammatory)
syndrome induced by adjuvants (ASIA).Methods:On the grounds
of preliminary investigations in 252 patients with alum-associated
ASIA showing both a selective increase of circulating CCL2, the
major monocyte chemoattractant, and a variation in the CCL2 gene, we
designed mouse experiments to assess biodistribution of
vaccine-derived aluminum and of alum-particle fluorescent surrogates
injected in muscle. Aluminum was detected in tissues by Morin stain
and particle induced X-ray emission) (PIXE) Both 500 nm fluorescent
latex beads and vaccine alum agglomerates-sized nanohybrids (Al-Rho)
were used.Results:Intramuscular injection of alum-containing
vaccine was associated with the appearance of aluminum deposits in
distant organs, such as spleen and brain where they were still
detected one year after injection. Both fluorescent materials
injected into muscle translocated to draining lymph nodes (DLNs) and
thereafter were detected associated with phagocytes in blood and
spleen. Particles linearly accumulated in the brain up to the
six-month endpoint; they were first found in perivascular CD11b+
cells and then in microglia and other neural cells. DLN ablation
dramatically reduced the biodistribution. Cerebral translocation was
not observed after direct intravenous injection, but significantly
increased in mice with chronically altered blood-brain-barrier.
Loss/gain-of-function experiments consistently implicated CCL2 in
systemic diffusion of Al-Rho particles captured by monocyte-lineage
cells and in their subsequent neurodelivery. Stereotactic particle
injection pointed out brain retention as a factor of progressive
particle accumulation.ConclusionNanomaterials can be
transported by monocyte-lineage cells to DLNs, blood and spleen,
and, similarly to HIV, may use CCL2-dependent mechanisms to
penetrate the brain. This occurs at a very low rate in normal
conditions explaining good overall tolerance of alum despite its
strong neurotoxic potential. However, continuously escalating doses
of this poorly biodegradable adjuvant in the population may become
insidiously unsafe, especially in the case of overimmunization or
immature/altered blood brain barrier or high constitutive CCL-2
production.

AbstractThe autism-mercury hypothesis first described
by Bernard et al. has generated much interest and controversy. The
Institute of Medicine (IOM) reviewed the connection between
mercury-containing vaccines and neurodevelopmental disorders,
including autism. They concluded that the hypothesis was
biologically plausible but that there was insufficient evidence to
accept or reject a causal connection and recommended a comprehensive
research program. Without citing new experimental evidence, a number
of observers have offered opinions on the subject, some of which
reject the IOM's conclusions. In a recent review, Nelson and Bauman
argue that a link between the preservative thimerosal, the source of
the mercury in childhood vaccines, is improbable. In their defense
of thimerosal, these authors take a narrow view of the original
hypothesis, provide no new evidence, and rely on selective citations
and flawed reasoning. We provide evidence here to refute the Nelson
and Bauman critique and to defend the autism-mercury hypothesis.

Autism
Spectrum Disorders in Relation to Distribution of Hazardous Air
Pollutants in the SF Bay AreaEnvironmental
Health Perspectives – Vol. 114 No. 9, September, 2006Gayle
Windham, Div. of Environmental and Occupational Disease Control,
California Department of Health Services284
ASD children & 657 controls, born in 1994 in Bay Area, were
assigned exposure levels by birth tract for 19 chemicals. Risks for
autism were elevated by 50% in tracts with the highest chlorinated
solvents and heavy metals. The highest risk compounds were mercury,
cadmium, nickel, trichloroethylene, and vinyl chloride, and the risk
from heavy metals was almost twice as high as solvents.Excerpt:
“Our results suggest a potential association between autism and
estimated metal concentrations, and possibly solvents, in ambient
air around the birth residence.”

Department of Psychiatry, The Ohio State University
Medical Center, Columbus, OH

AbstractObjectiveIn the
U.S., seasonal trivalent influenza vaccination (TIV) is currently
universally recommended for all pregnant women. However, data on the
maternal inflammatory response to vaccination is lacking and would
better delineate the safety and clinical utility of immunization. In
addition, for research purposes, vaccination has been used as a mild
immune trigger to examine in vivo inflammatory responses in
nonpregnant adults. The utility of such a model in pregnancy is
unknown. Given the clinical and empirical justifications, the
current study examined the magnitude, time course, and variance in
inflammatory responses following seasonal influenza virus
vaccination among pregnant women.MethodsWomen were assessed
prior to and at one day (n=15), two days (n=10), or approximately
one week (n=21) following TIV. Serum interleukin (IL)-6, tumor
necrosis factor (TNF)-α, C-reactive protein (CRP), and macrophage
migration inhibitory factor (MIF) were determined by high
sensitivity immunoassay.ResultsSignificant increases in CRP
were seen at one and two days post-vaccination (ps <.05). A
similar effect was seen for TNF-α, for which an increase at two
days post-vaccination approached statistical significance (p = .06).
There was considerable variability in magnitude of response;
coefficients of variation for change at two days post-vaccination
ranged from 122% to 728%, with the greatest variability in IL-6
responses at this timepoint.ConclusionsTrivalent influenza
virus vaccination elicits a measurable inflammatory response among
pregnant women. There is sufficient variability in response for
testing associations with clinical outcomes. As adverse perinatal
health outcomes including preeclampsia and preterm birth have an
inflammatory component, a tendency toward greater inflammatory
responding to immune triggers may predict risk of adverse outcomes,
providing insight into biological mechanisms underlying risk. The
inflammatory response elicited by vaccination is substantially
milder and more transient than seen in infectious illness, arguing
for the clinical value of vaccination. However, further research is
needed to confirm that the mild inflammatory response elicited by
vaccination is benign in pregnancy

Department of Psychiatry, Columbia University College of
Physicians and Surgeons, New York State Psychiatric Institute, New
York, NY, USA, Department of Epidemiology, Columbia University
Mailman School of Public Health, New York, NY, USA.

AbstractAutism
is a complex neuropsychiatric syndrome with a largely unknown
etiology. Inflammation during pregnancy may represent a common
pathway by which infections and other insults increase risk for the
disorder. Hence, we investigated the association between early
gestational C-reactive protein (CRP), an established inflammatory
biomarker, prospectively assayed in maternal sera, and childhood
autism in a large national birth cohort with an extensive serum
biobank. Other strengths of the cohort included nearly complete
ascertainment of pregnancies in Finland (N=1.2 million) over the
study period and national psychiatric registries consisting of
virtually all treated autism cases in the population. Increasing
maternal CRP levels, classified as a continuous variable, were
significantly associated with autism in offspring. For maternal CRP
levels in the highest quintile, compared with the lowest quintile,
there was a significant, 43% elevated risk. This finding suggests
that maternal inflammation may have a significant role in autism,
with possible implications for identifying preventive strategies and
pathogenic mechanisms in autism and other neurodevelopmental
disorders.Molecular Psychiatry advance online publication, 22
January 2013; doi:10.1038/mp.2012.197.

AbstractThere is a compelling argument that the
occurrence of regressive autism is attributable to genetic and
chromosomal abnormalities, arising from the overuse of vaccines,
which subsequently affects the stability and function of the
autonomic nervous system and physiological systems. That sense
perception is linked to the autonomic nervous system and the
function of the physiological systems enables us to examine the
significance of autistic symptoms from a systemic perspective.
Failure of the excretory system influences elimination of heavy
metals and facilitates their accumulation and subsequent
manifestation as neurotoxins: the long-term consequences of which
would lead to neurodegeneration, cognitive and developmental
problems. It may also influence regulation of neural hyperthermia.
This article explores the issues and concludes that sensory
dysfunction and systemic failure, manifested as autism, is the
inevitable consequence arising from subtle DNA alteration and
consequently from the overuse of vaccines.

Department of Pediatric
Rehabilitation of the Medical University of Bialystok,
Poland

AbstractThe present review summarizes data on
neurological adverse events following vaccination in the relation to
intensity, time of onset, taking into account the immunological and
non-immunological mechanisms. The authors described the
physiological development of the immune system and the possible
immune system responses following vaccination. Toxic property of
thimerosal - a mercury-containing preservative used in some vaccines
was presented. The neurological complications after vaccination were
described. The role of vaccination in the natural course of
infectious diseases and the current immunizations schedule in Poland
was discussed.

AbstractAutism Spectrum Disorders (ASD) are a
group of heterogeneous neurodevelopmental conditions presenting in
early childhood with a prevalence ranging from 0.7% to 2.64%. Social
interaction and communication skills are impaired and children often
present with unusual repetitive behavior. The condition persists for
life with major implications for the individual, the family and the
entire health care system. While the etiology of ASD remains
unknown, various clues suggest a possible association with altered
immune responses and ASD. Inflammation in the brain and CNS has been
reported by several groups with notable microglia activation and
increased cytokine production in postmortem brain specimens of young
and old individuals with ASD. Moreover several laboratories have
isolated distinctive brain and CNS reactive antibodies from
individuals with ASD. Large population based epidemiological studies
have established a correlation between ASD and a family history of
autoimmune diseases, associations with MHC complex haplotypes, and
abnormal levels of various inflammatory cytokines and immunological
markers in the blood. In addition, there is evidence that antibodies
that are only present in some mothers of children with ASD bind to
fetal brain proteins and may be a marker or risk factor for ASD.
Studies involving the injection of these ASD specific maternal serum
antibodies into pregnant mice during gestation, or gestational
exposure of Rhesus monkeys to IgG subclass of these antibodies, have
consistently elicited behavioral changes in offspring that have
relevance to ASD. We will summarize the various types of studies
associating ASD with the immune system, critically evaluate the
quality of these studies, and attempt to integrate them in a way
that clarifies the areas of immune and autoimmune phenomena in ASD
research that will be important indicators for future research.

AbstractGastrointestinal
symptoms are common in children with autism spectrum disorder (ASD)
and are often associated with mucosal inflammatory infiltrates of
the small and large intestine. Although distinct histologic and
immunohistochemical properties of this inflammatory infiltrate have
been previously described in this ASDGI group, molecular
characterization of these lesions has not been reported. In this
study we utilize transcriptome profiling of gastrointestinal mucosal
biopsy tissue from ASDGI children and three non-ASD control groups
(Crohn's disease, ulcerative colitis, and histologically normal) in
an effort to determine if there is a gene expression profile unique
to the ASDGI group. Comparison of differentially expressed
transcripts between the groups demonstrated that non-pathologic
(normal) tissue segregated almost completely from inflamed tissue in
all cases. Gene expression profiles in intestinal biopsy tissue from
patients with Crohn's disease, ulcerative colitis, and ASDGI, while
having significant overlap with each other, also showed distinctive
features for each group. Taken
together, these results demonstrate that ASDGI children have a
gastrointestinal mucosal molecular profile that overlaps
significantly with known inflammatory bowel disease (IBD), yet has
distinctive features that further supports the presence of an
ASD-associated IBD variant, or, alternatively, a prodromal phase of
typical inflammatory bowel disease.
Although we report qPCR confirmation of representative
differentially expressed transcripts determined initially by
microarray, these findings may be considered preliminary to the
extent that they require further confirmation in a validation
cohort.

AbstractCell-mediated
immune response to human myelin basic protein was studied by the
macrophage migration inhibition factor test in 17 autistic patients
and a control group of 11 patients suffering from other mental
diseases included in the differential diagnosis of the syndrome of
autism. Of the 17 autistic patients, 13 demonstrated inhibition of
macrophage migration, whereas none of the nonautistic patients
showed such a response. The
results indicate the existence of a cell-mediated immune response to
brain tissue in the syndrome of autism.

AbstractIt
has been reported that measles virus may be present in the intestine
of patients with Crohn's disease. Additionally, a new syndrome has
been reported in children with autism who exhibited developmental
regression and gastrointestinal symptoms (autistic enterocolitis),
in some cases soon after MMR vaccine. It is not known whether the
virus, if confirmed to be present in these patients, derives from
either wild strains or vaccine strains. In order to characterize the
strains that may be present, we have carried out the detection of
measles genomic RNA in peripheral mononuclear cells (PBMC) in eight
patients with Crohn's disease, three patients with ulcerative
colitis, and nine children with autistic enterocolitis. As controls,
we examined healthy children and patients with SSPE, SLE, HIV-1 (a
total of eight cases). RNA was purified from PBMC by Ficoll-paque,
followed by reverse transcription using AMV; cDNAs were subjected to
nested PCR for detection of specific regions of the hemagglutinin
(H) and fusion (F) gene regions. Positive samples were sequenced
directly, in nucleotides 8393-8676 (H region) or 5325-5465 (from
noncoding F to coding F region). One of eight patients with Crohn
disease, one of three patients with ulcerative colitis, and three of
nine children with autism, were positive. Controls were all
negative. The sequences obtained from the patients with Crohn's
disease shared the characteristics with wild-strain virus. The
sequences obtained from the patients with ulcerative colitis and
children with autism were consistent with being vaccine strains.
The results were concordant with the exposure history of the
patients. Persistence of measles virus was confirmed in PBMC in some
patients with chronic intestinal inflammation.

Neural Dynamics Research Group,
Department of Ophthalmology and Visual Sciences, University of
British Columbia, Vancouver, BC, Canada

Departments of
Ophthalmology and Visual Sciences and Experimental Medicine and the
Graduate Program in Neuroscience, University of British Columbia,
Vancouver, BC, Canada

Lucija Tomljenovic, Post-doctoral
fellow, Neural Dynamics Research Group, Department of Ophthalmology
and Visual Sciences, University of British Columbia

AbstractImmune
challenges during early development, including those
vaccine-induced, can lead to permanent detrimental alterations of
the brain and immune function. Experimental evidence also shows that
simultaneous administration of as little as two to three immune
adjuvants can overcome genetic resistance to autoimmunity. In some
developed countries, by the time children are 4 to 6 years old, they
will have received a total of 126 antigenic compounds along with
high amounts of aluminum (Al) adjuvants through routine
vaccinations. According to the US Food and Drug Administration,
safety assessments for vaccines have often not included appropriate
toxicity studies because vaccines have not been viewed as inherently
toxic. Taken together, these observations raise plausible concerns
about the overall safety of current childhood vaccination programs.
When assessing adjuvant toxicity in children, several key points
ought to be considered: (i) infants and children should not be
viewed as “small adults” with regard to toxicological risk as
their unique physiology makes them much more vulnerable to toxic
insults; (ii) in adult humans Al vaccine adjuvants have been linked
to a variety of serious autoimmune and inflammatory conditions
(i.e., “ASIA”), yet children are regularly exposed to much
higher amounts of Al from vaccines than adults; (iii) it is often
assumed that peripheral immune responses do not affect brain
function. However,
it is now clearly established that there is a bidirectional
neuro-immune cross-talk that plays crucial roles in immunoregulation
as well as brain function. In turn, perturbations of the
neuro-immune axis have been demonstrated in many autoimmune diseases
encompassed in “ASIA” and are thought to be driven by a
hyperactive immune response; and (iv) the same components of the
neuro-immune axis that play key roles in brain development and
immune function are heavily targeted by Al adjuvants.
In summary, research evidence shows that increasing concerns about
current vaccination practices may indeed be warranted. Because
children may be most at risk of vaccine-induced complications, a
rigorous evaluation of the vaccine-related adverse health impacts in
the pediatric population is urgently needed.

AbstractThimerosal is an organic mercury compound
that is widely used as a preservative in vaccines and other solution
formulations. The use of thimerosal has caused concern about its
ability to cause neurological abnormalities due to mercury
accumulation during a normal schedule of childhood vaccinations.
While the chemistry and the biological effects of methylmercury have
been well-studied, those of thimerosal have not. Thimerosal reacted
rapidly with cysteine, GSH, human serum albumin, and single-stranded
DNA to form ethylmercury adducts that were detectable by mass
spectrometry. These results indicated that thimerosal would be
quickly metabolized in vivo because of its reactions with protein
and nonprotein thiols. Thimerosal
also potently inhibited the decatenation activity of DNA
topoisomerase II alpha, likely through reaction with critical free
cysteine thiol groups.
Thimerosal, however, did not act as a topoisomerase II poison and
the lack of cross-resistance with a K562 cell line with a decreased
level of topoisomerase II alpha (K/VP.5 cells) suggested that
inhibition of topoisomerase II alpha was not a significant mechanism
for the inhibition of cell growth. Depletion
of intracellular GSH with buthionine sulfoximine treatment greatly
increased the K562 cell growth inhibitory effects of thimerosal,
which showed that intracellular glutathione had a major role in
protecting cells from thimerosal.
Pretreatment of thimerosal with glutathione did not, however, change
its K562 cell growth inhibitory effects, a result consistent with
the rapid exchange of the ethylmercury adduct among various
thiol-containing cellular reactants. Thimerosal-induced single and
double strand breaks in K562 cells were consistent with a rapid
induction of apoptosis. In conclusion, these studies have elucidated
some of the chemistry and biological activities of the interaction
of thimerosal with topoisomerase II alpha and protein and nonprotein
thiols and with DNA.

AbstractTopoisomerases are
expressed throughout the developing and adult brain and are mutated
in some individuals with autism spectrum disorder (ASD). However,
how topoisomerases are mechanistically connected to ASD is unknown.
Here we find that topotecan, a topoisomerase 1 (TOP1) inhibitor,
dose-dependently reduces the expression of extremely long genes in
mouse and human neurons, including nearly all genes that are longer
than 200 kilobases. Expression of long genes is also reduced after
knockdown of Top1 or Top2b in neurons, highlighting that both
enzymes are required for full expression of long genes. By mapping
RNA polymerase II density genome-wide in neurons, we found that this
length-dependent effect on gene expression was due to impaired
transcription elongation. Interestingly, many high-confidence ASD
candidate genes are exceptionally long and were reduced in
expression after TOP1 inhibition. Our
findings suggest that chemicals and genetic mutations that impair
topoisomerases could commonly contribute to ASD and other
neurodevelopmental disorders.

AbstractWe have examined the neurotoxicity of aluminum
in humans and animals under various conditions, following different
routes of administration, and provide an overview of the various
associated disease states. The literature demonstrates clearly
negative impacts of aluminum on the nervous system across the age
span. In adults, aluminum exposure can lead to apparently
age-related neurological deficits resembling Alzheimer's and has
been linked to this disease and to the Guamanian variant, ALS-PDC.
Similar outcomes have been found in animal models. In addition,
injection of aluminum adjuvants in an attempt to model Gulf War
syndrome and associated neurological deficits leads to an ALS
phenotype in young male mice. In young children, a highly
significant correlation exists between the number of pediatric
aluminum-adjuvanted vaccines administered and the rate of autism
spectrum disorders. Many of the features of aluminum-induced
neurotoxicity may arise, in part, from autoimmune reactions, as part
of the ASIA syndrome.

AbstractThimerosal
is a vaccine antimicrobial preservative which has long been
suspected an iatrogenic factor possibly contributing to
neurodevelopmental disorders including autism. The association
between infant vaccine thimerosal exposure and autism remains an
open question. Although thimerosal has been removed from mandatory
childhood vaccines in the United States, thimerosal-preserved
vaccines are still widely used outside of the United States
especially in developing countries. Notably, thimerosal-containing
vaccines are being given to the newborns within the first 12-24 h
after birth in some countries. To examine the possible neurotoxic
effects of early neonatal exposure to a higher level of thimerosal,
FVB mice were subcutaneously injected with thimerosal-mercury at a
dose which is 20× higher than that used for regular Chinese infant
immunization during the first 4 months of life. Thimerosal-treated
mice exhibited neural development delay, social interaction
deficiency, and inclination of depression. Apparent
neuropathological changes were also observed in adult mice
neonatally treated with thimerosal. High-throughput RNA sequencing
of autistic-behaved mice brains revealed the alternation of a number
of canonical pathways involving neuronal development, neuronal
synaptic function, and the dysregulation of endocrine system.
Intriguingly, the elevation of anterior pituitary secreting hormones
occurred exclusively in male but not in female thimerosal-treated
mice, demonstrating for the first time the gender bias of
thimerosal-mercury toxicity with regard to endocrine system. Our
results indicate that higher dose of neonatal thimerosal-mercury
(20× higher than that used in human) is capable of inducing
long-lasting substantial dysregulation of neurodevelopment, synaptic
function, and endocrine system, which could be the causal
involvements of autistic-like behavior in mice.

AbstractEmerging research
suggests that the timing of environmental factors in the presence of
genetic predispositions has influenced the increase in autism
spectrum disorders over the past several decades. A review of the
medical literature suggests that autism may be impacted by
environmental toxicants, breastfeeding duration, gut flora
composition, nutritional status, acetaminophen use, vaccine
practices and use of antibiotics and/or frequency of infections. The
author reports her retrospective clinical research in a general
pediatric practice (Advocates for Children), which shows a modest
trend toward lower prevalence of autism than her previous pediatric
practice or recent CDC data. Out of 294 general pediatrics patients
followed since 2005 there were zero new cases of autism (p value
0.014). Given the prevalence of autism for that cohort of 1 in 50
children in the United States, it is important to consider
implementing strategies in primary care practice that could
potentially modify environmental factors or affect the timing of
environmental triggers contributing to autism.

AbstractUniversal hepatitis
B vaccination was recommended for U.S. newborns in 1991; however,
safety findings are mixed. The association between hepatitis B
vaccination of male neonates and parental report of autism diagnosis
was determined. This cross-sectional study used weighted probability
samples obtained from National Health Interview Survey 1997-2002
data sets. Vaccination status was determined from the vaccination
record. Logistic regression was used to estimate the odds for autism
diagnosis associated with neonatal hepatitis B vaccination among
boys age 3-17 years, born before 1999, adjusted for race, maternal
education, and two-parent household. Boys
vaccinated as neonates had threefold greater odds for autism
diagnosis compared to boys never vaccinated or vaccinated after the
first month of life.
Non-Hispanic white boys were 64% less likely to have autism
diagnosis relative to nonwhite boys. Findings suggest that U.S. male
neonates vaccinated with the hepatitis B vaccine prior to 1999 (from
vaccination record) had a threefold higher risk for parental report
of autism diagnosis compared to boys not vaccinated as neonates
during that same time period. Nonwhite boys bore a greater risk.

While those that deny the constancy of chemical properties; ie. mercury has for thousands of years been known to take your mind away, they can take comfort from the millions in sponsorship from vaccine companies.

There is always someone, somewhere, shining and laughing at us and rolling in money if not things they made themselves.

I don't think there is any April Fool on David Tayloe here but on those that have to put up with lies, obfuscation and after the destruction of their child by vaccines get insulted with taunts of you are putting our vaccine schedule at risk by spreading the truth about these products. They at the same time spread lies that these people with autism do not support vaccines. Well how did their child get autistic? They did support vaccines for their child, found out the truth and cannot be faulted for saying NOTHING.

Charles Richet 1913 - repeat vaccines induce anaphylaxis and death.

Insert for modern vaccine - this product was tested briefly in a small trial and killed more than a dozen of those it was tested on. It has therefore been passed with flying colours for younger, sicker, immune compromised children where it will not be expected to kill anyone that can't be explained away in like fashion ie; SIDS.

SIDS does have 11 out of 12 clinical signs of vaccine harm but with "expert" medico-legal testimony these people can be incarcerated for life if they complain.

I would encourage you to check into two additional areas of research & papers:

(1) V.K. Singh et al, on studies finding antibodies to MBP in association with the measles virus from the MMR vaccine in the damaged guts of kids diagnosed w/ASD. The case: The measles virus component is cultured on chick embryo cells; they can contain MBP; MBP is MBP. Thus the vaccine triggers an autoimmune reaction to the child's own MBP. Thus the vaccine damages the myelin sheathing to the cranial nerve systems; it also damages the gut, leading to the leaky gut syndrome that allows the viruses (& other peptides/toxins) into the bloodstream, and crossing the damaged BBB...

(2) Live-virus vaccines contain glutamate/glutamic acid (it's a stabilizer). Glutamate lowers glutathione levels. Thus, such a vaccine given at the same time as others containing thimerosal or aluminum...

I'm sorry I don't have specific references to hand. But the MSG angle can be obtained at msgtruth.com. Carol Hornlein has done excellent work in this regard.

Keep up your own excellent work. We're getting there, thanks to parents like you, and the docs willing to work w/the protocols.

I look forward to an actual doctor reviewing your list, but off the top of my head, most of your "proof" here seems to either be completely unrelated to the question at hand or fall under the logical fallacy of "begging the question."

Yes, if you assume that vaccines cause heavy metal poisoning, then vaccines might cause autism...but I haven't seen any evidence of vaccines causing heavy metal poisoning!

"most of your "proof" here seems to either be completely unrelated to the question at hand or fall under the logical fallacy of "begging the question."

And that is because you have not even stopped to learn about what the basic mechanisms of the biological processes at work in vaccine regression and autism are.

While your group has camped in "correlation does not equal causation" land, we have gone on with out you and an entire field of medicine has sprung up on this topic that is ignored by Mr. Mnookin and those who want our children to stay sick.

Wonderful, Ginger! Thank you so much. I've been lecturing nationally on the vaccine scam for eight years, mostly to health professionals, and this will be a great asset to future teachings. I would simply add that the causal autism link is not only due to mercury, but to the immune overstimulation form multiple pathogens (Blaylock's work). With much appreciation, Michael Gaeta, DAc, www.gaetacommunications.com

thank you Ginger for a quick list we can all share. We are making progress. Last night at a birthday party a new mother told me they went to the health department and got a religious exemption for their daughter. Based on what they saw of my flu shot reaction and the information we share.

Thanks for this comprehensive collection...the findings are extremely worrying for children and their parents. It is obvious that a health program that once had some genuine benefit to childrens health now ironically carries a serious risk to it.

just wanted to let you know that you should leave quoting science papers to people who understand science papers. I doubt that you did so out of malevolence, but it really doesn't matter.

Many of these papers have nothing to do with what you're claiming they mean, and the others are deliberately feeding on the anti-vaccer zeal. For example every article is missing something important like sample size, margin of error, or general god damn method. As you highlight so well, they just tell you the conclusion you want to hear. You don't highlight methods or data, you highlight the part that says the conclusion you had before you looked at the paper. This is not science, and this is going to be a long hard debate because of places like this misrepresenting actual science.

Oh my god. Classic anti-vaccine post! I was excited to see some real science backing one of these anti-vaccine claims (I've never been able to find anything reputable) but lo and behold when I actually looked at them what you highlight in most cases it has NOTHING to do with vaccines. I love how you just say "these articles show x" and all these people believe it! Clearly our education system is in shambles.

As long as uninformed people continue to fuel the "vaccines cause autism" lie we are being distracted from finding the REAL causes of Autism.

I know you won't post this because it doesn't support your propaganda but I at least want you to know that informed people can see how wrong you are and you might want to get some better evidence to back you up.

Ginger,"Basic mechanisms of the bioligical processes at work in vaccine regression and autism"Could you point me to a credible source that has definitively established this and how it relates to multiple ASD diagnoses? I figure since you feel one needs a firm grasp of these processes to understand and interpret how these studies are accurately potraying a causal correlation with ASD,your audience and I need good credible sources from those in that field of study to figure out those processes. I'll catch up when you stop skipping steps in the scientific process.

It is a few years old, and more research has been published since the book, but it ties things together, and shows the successful treatments based on this view of what is currently diagnosed as "autism."

Andrew Wakefield's Thoughtful House's Bryan Jepson? The emergency physician, Bryan Jepson, that works with Russell Jepson, a chiropractor?What gives us reasonable insight into believing he is giving proper knowledge of the scientific process involved into determining "basic mechanisms of the biological processes at work in vaccine regression and autism" or a causative correlation between vaccines and multiple forms of ASD?What potential conflicts of interest may be present? What are his funding sources for "research"? And what is preventing him from taking the proper routes of transparent scientific investigation? Are his claims data-based or speculation?

Instead of being a jerk... how about you read the book, talk to people who have used the information in the book to improve the lives and functioning of children (and adults) with the physical syndromes described.

I have written at length that I have had quite enough of assholes who could not care less about our kids, behaving like you are behaving now. I am long since done with bad faith players like yourself.

Don't accept the research, the published body of evidence, the tens of thousands of cases of vaccine regression, ASD dx and recover using this understanding?

I DON'T CARE!

You are a bad faith player. Dow what you want, believe what you want... Just go away.

Ginger, I came across an article yesterday on my news feed about vaccines causing autoimmune diseases. http://naturalsociety.com/publicized-study-vaccination-schedule-bombshell/ provides a link to the paper: http://www.plosone.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0008382&representation=PDF Article is way over my head, but wanted to let you know about it.

I came across this article in my news feed on facebook yesterday: http://naturalsociety.com/publicized-study-vaccination-schedule-bombshell/ Here is the link to the study it references: http://www.plosone.org/article/fetchObject.action?uri=info%3Adoi%2F10.1371%2Fjournal.pone.0008382&representation=PDF

I think it's hilarious people are trying to discount evidence saying it's not what the original article intended. You find facts that correlate to come to a conclusion, If your researching I don't know lets say dog vitamins, you don't discount something a veterinarian says about canine nutrition because he wasn't directly correlating the topic with vitamins, the information remains well... informative.

I think the emotions surrounding this subject have greatly hindered discussion of this topic in a meaningful way. That being said, those emotions are understandable because those who support vaccination and those who are against it are both fighting for the same thing, and that is the welfare of children.

Even if we disagree with each other on this topic we both feel that the safety of children is paramount and I respect your fervor on this matter. I believe that those who have attacked you have only done so because they feel that not vaccinating children leads to serious harm. I also believe that you feel very strongly that these vaccinations cause serious harm.

I don't think that anyone here is stupid so I would simply like to provide this rather comprehensive report by the FDA for your consideration. It cites its sources so you can check them yourself if you distrust the intentions of the FDA.

Of particular interest I think is the table that contains the levels of mercury in vaccines on the market.

If you check it you'll see that mercury is no longer present in any significant amount in most vaccines and for those where it is present there is usually a mercury free alternative.

Therefore, I just want to say if you're concerned that thimersosal will harm your child, it would appear that you no longer have to worry about it and you can in good conscience vaccinate your child against diseases that could seriously harm it.

9e121712-5f87-11e3-98de-000bcdcb8a73, the FDA does have our best interest at heart, so thank you, but no thank you. If you think the FDA is interested in protect us.... I have some swamp land I'de like to sell you!

"The FDA 'protects' the big drug companies and are subsequently rewarded, and using the government's police powers they attack those who threaten the big drug companies. People think that the FDA is protecting them.

Whatever it is that causes autism , that's not important, the evidence is clearly in the fact that thousands , no hundreds of thousand of parents have seen an immediate connection with vaccinating and damage to their children . The stupid ' so called scientists cannot find the link so it does not exist . Stop vaccinating and the problem will go away . Don't reply please about the seriousness of the diseases of the past and how they will return when we stop vaccinating, it just will not happen as disease has moved on , we see a lot of diseases never heard of a hundred years ago , while still concentrating on diseases of the past. Stop vaccinating and build true immunity !

As always Ginger is spot on. Thank you so much Ginger. So sad we still have the deceived & those working to deceive to bury in truth. While this goes on we lose more & more children to the damage vaccines really represents. Proper research is getting done & more & more join the right side of this battle daily. My whole family has changed their minds. They have been paying attention. I was frustrated when they would not hear me a handful of years ago. Now that many have woke they have heard others so now they believe thanks to people like Ginger. Love you Ginger!

I have never seen someone contradict themselves so quickly! Just two short sentences!

In sentence one you dismiss the 84 papers above that show a correlations between autism and vaccines saying that, "Correlation does not equal causation."

The in sentence two, you suddenly reverse your claim that "Correlation does not equal causation." by saying that the correlation of gene mutations to autism is causal! "There's a gene that causes autism."

So to sum up... if research shows that vaccines correlate to autism, ignore it, but if research shows that genes correlate to autism, IT IS EQUALS CAUSATION!

You need to work on your consistency.

In fact, both correlate to autism, but IMHO there is much more evidence that vaccines are the larger problem... because as the authors of the study correctly note:

"Only about 15% of children with ASD have been found to have non-inherited mutations in these genes, and the remaining 85% must have other causes."

And there is no research on this (there should be) but just from parental reports, I think that the number of cases with vaccine involvement is much higher than 15%. Probably higher than 50%. But unless the research community wants to start doing real vaccine research, we won't know for sure.

Everyone who is seriously involved in this debate agrees that autism is caused by a COMBINATION of genetic and environmental factors.

And it may well be that the genetics, as the article discussed are not really inherited genes but mutations of a child's genes, we need to evaluate the possibility that the genetic damage itself is being cause by toxic environmental factors (including vaccines)

But here is what we can know...

That if to get autism you have to have BOTH genetic predisposition AND environmental insult, then why are we not focued on removing the toxic injury, because then the gene is not really a problem, is it?

So we are back to vaccines. We do not screen children for their vulnerability for vaccine injury, toxic injury... any of it.

So please understand, if you Big Medicine is not going to tell me if my child is one of the ones at risk, why would I participate in their program?

Gosh so much misinformation here. And still talks about vaccines containing mercury blah blah blah. When thiomerosal 1. Is no longer found in childhood vaccines2. Is not mercury! But a mercury compound.

I suggest you take a look at this list of studieshttp://www2.aap.org/immunization/families/faq/vaccinestudies.pdf

or even this very recent one from 2014http://www.sciencedirect.com/science/article/pii/S0264410X14006367

"Gosh so much misinformation here. And still talks about vaccines containing mercury blah blah blah. When thiomerosal 1. Is no longer found in childhood vaccines"

- So screw the US children who are mercury toxic and never evaluate or treat them for it? And screw the international children who are still getting it?

"2. Is not mercury! But a mercury compound."

-Which contains mercury. Which causes... well many horrible things.

"I suggest you take a look at this list of studieshttp://www2.aap.org/immunization/families/faq/vaccinestudies.pdf"

- These studies have been debated for many years, and I have reviewed many of them on the site here. Please feel free to go back through the blog.

"or even this very recent one from 2014http://www.sciencedirect.com/science/article/pii/S0264410X14006367"

- Which is just a rehash of all the previous studies that parents don't trust because they range from asking the wrong questions to being junk to being outright fraud. We laughed when we read it.

My thoughts are that after ten years I really am kind of over trolling comments like this one, and please let me know if you want to have an earnest conversation rather than making a dismissive "misinformation" comment that is supposed to wipe away almost a hundred studies that put together a large part of the autism "puzzle."

http://justthevax.blogspot.com/2014/03/75-studies-that-show-no-link-between.html First off, the evidence for your case doesn't bear out as well as you'd like. Second, even if it were true, would you honestly assert that an increase in the rate of autism is worth the chance of more dead and disabled children. My issue with this movement is the all of nothing of it, the extremism is the wrong stance. Its good to know that this anti vax thing is being promoted by a conservative. Now I can refute people who claim this is the lefts version of climate change denial. Thanks you.

One of the original 5 forms of autism was Pervasive Child Disorder. It was not caused by vaccines. The fact that it triggered around the ages of early vaccinations has been found to be coincidental. You and other parents like you are only doing untold amounts of damage with your misplaced rage over your children. It is unknown what actually triggers PCD, but it's known that it's NOT vaccines.